Journal of Obstetrics and Gynaecology, January 2014; 34: 1–7 © 2014 Informa UK, Ltd. ISSN 0144-3615 print/ISSN 1364-6893 online DOI: 10.3109/01443615.2013.817981
REVIEW
The role of laparoscopy in the management of infertility H. Hassa & Y. Aydin
J Obstet Gynaecol Downloaded from informahealthcare.com by V U L Periodicals Rec on 10/04/14 For personal use only.
Reproductive Medicine Unit, Department of Obstetrics and Gynaecology, Eskisehir Osmangazi University Medical Faculty, Eskisehir, Turkey
The advancement of new perspectives in assisted reproductive technology (ART) through the use of modern infertility evaluation techniques has led clinicians to reassess how infertility should best be treated. The usefulness of laparoscopy in the diagnostic work-up of infertile patients or in patients who are unresponsive to fertility treatments is debatable. The purpose of this review is to define the role of laparoscopy in the management of infertility, which is one of the most controversial aspects of reproductive medicine. To the best of our knowledge, laparoscopy is currently not a routine step in the evaluation of infertile women; every patient and clinical condition must be assessed individually. In this review, we investigated the effectiveness and the utility of laparoscopy as a diagnostic and therapeutic tool in the management of infertility. Various topics and parameters in ART will be discussed based on the evidence that is currently available. Keywords: Assisted reproductive technology, fertility, laparoscopy
Introduction In the 1990s, laparoscopy was the final step in the routine diagnostic approach for the evaluation of infertile couples (Rowe et al. 1993). However, due to the advancement of new perspectives in assisted reproductive technology (ART), the process of evaluating infertile couples has changed. Currently, the most widely accepted approach to infertility is no longer based on diagnosing an exact aetiology. The scope and the sequence of modern infertility evaluation focus on the most efficient and cost-effective tests. The investigation of infertile couples should be rapid and inexpensive, using minimally invasive tests (Gomel and McComb 2010). In addition, the focus of treatment for infertility has shifted from the systematic correction of each identified factor to applying the most efficient therapy, which may be ART (Speroff and Fritz 2011). The most common initial diagnostic tests for the evaluation of an infertile couple are the mid-luteal phase progesterone assay; a test for tubal patency, such as hysterosalpingography (HSG) for females and semen analysis for males. Laparoscopy is reserved for further diagnosis or may be used in combination with endoscopic surgery (Crosignani and Rubin 2000). Therefore, ART may be performed on suboptimally investigated couples. In cases of treatment failure or ART failure, secondary invasive diagnostic approaches, such as laparoscopy, are typically performed. The most important advantages of a limited evaluation of infertile couples, which excludes laparoscopy in the diagnostic work-up, are the prevention of a delay in treatment and minimal initial testing. However, a disadvantage of this approach is that
abnormalities that are associated with subfertility can be overlooked. In-vitro fertilisation (IVF) clinicians generally discount diagnostic laparoscopy (Bosteels et al. 2007). The aim of this review is to describe recent changes in the use of laparoscopy for diagnostic and therapeutic purposes in the treatment of infertility and specify the clinical conditions under which laparoscopy may be safely used as a diagnostic test in infertile couples. The effectiveness and the utility of laparoscopy will be discussed in various ART topics and parameters, based on the evidence that is currently available. In general, diagnostic laparoscopy may be used for otherwise unexplained infertility in the following circumstances: • To demonstrate tubal patency • To determine treatment before intrauterine insemination (IUI) or after IUI cycle failure. However, laparoscopy may be performed for diagnostic purposes and with therapies for fertility, in infertile couples who have any of the following conditions: • • • • •
Endometriosis After failed IVF Significant pelvic adhesions Hydrosalpinges Polycystic ovarian syndrome (PCOS).
Tubal patency HSG is the most widely used test for the evaluation of infertile couples to determine tubal patency. HSG can be used to test tubal patency and for a morphological evaluation of the tubes and uterus. In addition to normal morphological findings, HSG can detect tubal occlusion, lesions (salpingitis isthmica nodosa or endometriosis) and intratubal architecture (dilatation, rugae and intratubal adhesions) (Gomel 2010; Gomel and Taylor 1995). For detecting tubal patency, HSG has a moderate sensitivity of 65% and a relatively high specificity of 83% (Evers et al. 2003; Swart et al. 1995). The clinical implications of an obstruction that is detected by HSG, include a high probability that the tube is open (approximately 60%); however, when HSG shows patency, there is a low probability that the tube is occluded (approximately 5%). Generally, the rate of treatment-independent pregnancy is highest when both tubes are patent, according to HSG (Speroff and Fritz 2011). However, laparoscopy provides a general view of the pelvic organs and any bowel and/or pelvic peritoneal adhesions; therefore, this procedure may be used to identify milder forms of distal
Correspondence: Y. Aydin, Reproductive Medicine Unit, Department of Obstetrics and Gynaecology, Eskisehir Osmangazi University Medical Faculty, Eskisehir, 26000, Turkey. E-mail: [email protected]
J Obstet Gynaecol Downloaded from informahealthcare.com by V U L Periodicals Rec on 10/04/14 For personal use only.
2
H. Hassa & Y. Aydin
tubal occlusive diseases, such as fimbrial agglutination or fimbrial phimosis. In addition, we can detect minimal and mild endometriosis, which may not be detected on pelvic ultrasonography (USG) or HSG. Most importantly, at the time of diagnosis, diseases may be treated laparoscopically. In pelvic adhesive diseases, which are caused by pathological factors (endometriosis or pelvic infection), tubal patency can be demonstrated by the passage of contrast media using HSG; however, tubal fimbriae function, which primarily determines fertility, cannot be properly demonstrated. In addition to tubal patency, tubal functions, such as free fimbrial movement, are necessary for ovum capture and fertilisation. Even in the presence of open fallopian tubes, as detected by HSG, deficient fimbrial movement that is inadequate for ovum retrieval may cause infertility. Therefore, laparoscopy is an exceptional test that can determine fimbrial function in addition to the patency of tubes, which is vital for ovum retrieval (Speroff and Fritz 2011). Using laparoscopy, the prognosis of patients is best when both fallopian tubes are patent, poor when both tubes are blocked and intermediate when only one tube is open (Maas et al. 1997; Mol et al. 1999). When testing for tubal patency, false-negatives in HSG are more common than in laparoscopy. Consequently, tubal blockages detected by HSG are often false-positives; however, obstructions diagnosed by laparoscopy are most likely truepositives. Therefore, the prognosis of a tubal obstruction (unilateral and/or bilateral) is poorer when diagnosed with laparoscopy than with HSG (Speroff and Fritz 2011). In a large prospective cohort study, Mol et al. (1999) demonstrated that unilateral and bilateral tubal occlusion, as determined by HSG and laparoscopy, were associated with treatmentindependent pregnancy. After a normal or unilateral occlusion was detected by HSG, laparoscopy revealed a bilateral occlusion in 5% of patients, and the probability of fertility in these patients was zero. The likelihood of fertility in the cases with a bilateral occlusion according to HSG was significantly reduced when laparoscopy indicated a unilateral or bilateral occlusion. The authors recommended that laparoscopy be postponed until at least 10 months after normal or unilateral abnormal HSG, whereas laparoscopy provides useful information when performed immediately after bilateral abnormal HSG. However, when deciding whether to delay laparoscopy for 10 months, clinicians must consider other prognostic factors, particularly the age of the patient. In females 36 years of age, IVF success rates begin to decline; therefore, a delay in a diagnosis is not acceptable (Templeton et al. 1996; Van Kooij et al. 1996). Laparoscopy is recommended when HSG reveals a bilateral obstruction. This procedure can be postponed for at least 10 months after normal patency or a unilateral obstruction is revealed by HSG, especially in females 36 years of age. In contrast, if HSG indicates patency in one or both tubes and the patient has a history of pelvic infection, ectopic pregnancy, tubal surgery or symptoms of endometriosis, the patient should be offered laparoscopy. For patients with a history of tuberculosis or severe pelvic infection, laparoscopy should be considered as a first-step approach instead of HSG because in these clinical conditions, tubal morphology and fimbrial functional capacity are more important than demonstrating tubal patency.
The role of laparoscopy in IUI cycles IUI is generally the standard treatment option for unexplained infertility and mild male factor infertility. After the standard diagnostic work-up, which includes HSG, clinicians primarily treat these patients with expectant management or IUI controlled ovarian stimulation (Wordsworth et al. 2011). However, treatment
failure presents a dilemma: either continue with additional diagnostic procedures, such as laparoscopy, or proceed directly with ART. Clinicians typically encounter this quandary before IUI treatment failure. Current treatments, such as empirical clomiphene citrate and unstimulated IUI, are costly and do not lead to increased live birth rates compared with expectant management of unexplained infertility (Wordsworth et al. 2011). Tanahatoe et al. (2003) retrospectively analysed the role of diagnostic laparoscopy in the evaluation of infertility before IUI. They investigated the prevalence of laparoscopic findings that led to a change in treatment decisions before IUI in 495 patients with normal HSG. Laparoscopy revealed pathological abnormalities, such as endometriosis and adhesions, in 35% of the patients and the initial treatment decisions were changed in 25% of the patients. Overall, 21% of the patients had laparoscopic abnormalities that were treated directly during laparoscopy, followed by IUI treatment. Additionally, 4% of patients had severe pathologies and IVF or secondary surgery was recommended. In a randomised controlled trial, Tanahatoe et al. (2005) compared the accuracy of standard laparoscopy before IUI with laparoscopy that was performed after six unsuccessful cycles of IUI. A total of 154 patients were equally randomised into a diagnostic laparoscopy first (DLSF) group or an IUI first (IUIF) group. Abnormal findings detected during laparoscopy (adhesiolysis, vaporisation of endometriosis, and fimbriolysis), which required treatment, were comparable in the DLSF and IUIF groups (48% compared with 56%; p 0.63; OR 1.4; 95% CI 0.5–3.6). The on-going pregnancy rate in the DLSF group was 44% compared with 49% in the IUIF group (p 0.63; OR 1.2; 95% CI 0.7–2.3). There were three major endpoints from this study. First, performing laparoscopy before IUI did not increase the on-going pregnancy rate. Second, the number of abnormalities that required laparoscopic intervention was not significantly higher in the group who underwent laparoscopy after 6 cycles of IUI compared with the group who underwent immediate laparoscopy before IUI. Third, 48% of the DLSF group and 56% of the IUIF group had abnormal findings during laparoscopy that resulted in a laparoscopic intervention. These rates were higher than a previously detected total abnormality rate of 35%. After combining live birth rates and on-going pregnancies after 20 weeks, a 2010 Cochrane meta-analysis demonstrated the superiority of laparoscopic surgery over diagnostic laparoscopy in the presence of minimal and mild endometriosis (Jacobson et al. 2010). The odds ratio (OR) was 1.64 (95% CI 1.05–2.57) in favour of laparoscopic surgery. Further randomised controlled trials are warranted to determine whether laparoscopy should be performed with IUI and whether this procedure should be performed before or after IUI. We believe that an indication for diagnostic laparoscopy before IUI should be confirmed in the presence of a history of pelvic infection, ectopic pregnancy, tubal surgery or symptoms of endometriosis.
The role of laparoscopy in endometriosis Endometriosis is significantly associated with infertility. The prevalence of endometriosis in the infertile patient population is higher (48%) compared with women who undergo tubal sterilisation (5%) (Strathy et al. 1982). Randomised controlled trials have demonstrated that the clinical pregnancy rate after ovarian stimulation or ovarian stimulation IUI was significantly lower in women with minimal and mild endometriosis, than in women with unexplained infertility (Nuoja-Huttunen et al. 1999; Omland et al. 1998). However, controlled trials revealed that the clinical pregnancy rate after ovar-
J Obstet Gynaecol Downloaded from informahealthcare.com by V U L Periodicals Rec on 10/04/14 For personal use only.
Laparoscopy in infertility ian stimulation IUI was higher in women who had received an ablation of endometriotic lesions before ovarian stimulation IUI (Deaton et al. 1990; Tummon et al. 1997). In a multi-centre trial in Canada, women who had minimal and mild endometriosis on diagnostic laparoscopy were randomised to undergo either excision–ablation of endometriotic lesions or expectant management. Laparoscopic surgery increased the cumulative probability of a pregnancy that lasted more than 20 weeks in the first 36 weeks after the procedure (cumulative incidence ratio, 1.7; 95% CI, 1.2–2.6) (Marcoux et al. 1997). In a smaller study in Italy, women with endometriosis-associated infertility were similarly randomised into a laparoscopic surgery group (excision or ablation of endometriotic lesions) or an expectant management group and were followed up for 1 year after laparoscopy. The 1-year birth rates were 19.6% in the resection–ablation group and 22.2% in the expectant management group (Parazzini 1999). In contrast with larger trials in Canada, the results of this study did not support the hypothesis that ablation of endometriotic lesions markedly improves fertility rates. A recent Cochrane meta-analysis, which included studies in Canada and Italy, demonstrated the superiority of laparoscopic surgery over diagnostic laparoscopy according to the on-going pregnancy rate at 20 weeks, the live birth rate with an OR of 1.64 (95% CI, 1.05–2.57) and the clinical pregnancy rates with an OR of 1.66 (95% CI, 1.09–2.51), which favoured laparoscopic surgery (Jacobson et al. 2010). In a retrospective cohort study, Opøien et al. (2011) evaluated the effects of laparoscopic surgery (using ablation of endometriotic lesions) on subsequent IVF/ICSI treatment. Compared with women who only received diagnostic laparoscopy, women who underwent the complete removal of endometriotic lesions had a significantly improved implantation rate (30.9% vs 23.9%, p 0.02), pregnancy rate (40.1% vs 29.4%, p 0.004) and livebirth rate per oocyte retrieval (27.7% vs 20.6%, p 0.04). The surgical removal of minimal and mild endometriotic lesions reduced the time to first pregnancy and resulted in a higher cumulative pregnancy rate. In contrast with minimal and mild endometriosis, distorted anatomy and chronic inflammatory conditions are more predominant in severe endometriosis. The intent of surgery in infertile patients who are affected by moderate to severe endometriosis is to restore normal anatomy through the extirpation of the disease and careful adhesiolysis (Busacca and Olive 2010). This type of surgery will most likely increase the chance of spontaneous conception (Somigliana et al. 2006a,b). In addition, the complete and thorough microsurgical eradication of endometriosis may result in increased spontaneous pregnancies and IVF pregnancies, even after multiple failed IVF cycles (Littman et al. 2005). No prospective studies have compared expectant management and fertility treatment in ART or surgery; however, several case studies have been reported. In these studies, the cumulative pregnancy rate after 1–3 years of surgical treatment was 50% for women with endometriomas and approximately 30% for women with complete cul-de-sac obliteration (Adamson and Pasta 1994; Donnez et al. 1996). One of the most debatable issues regarding the management of endometriosis with IVF, is the presence of an endometrioma. Endometriomas lower pregnancy success rates; however, surgery similarly adversely affects IVF results (Busacca and Olive 2010). An appropriate study design to evaluate the effect of endometriomas on oocyte numbers includes monitoring the response of the ovary with the endometrioma to ovarian stimulation during IVF/ICSI cycles and using the contralateral normal ovary of the same patient as a control. Somigliana et al. (2006a) conducted this type of study in 59 ICSI cycles in 36 patients who had unilateral
3
ovarian endometriomas and who did not undergo previous ovarian surgery. The numbers of co-dominant follicles in intact and affected ovaries (ovaries with an endometrioma) were 4.0 2.2 and 3.0 1.7, respectively (p 0.01). This difference was correlated with a mean reduction of 25% (6–44%) (Somigliana et al. 2006b). This deleterious effect was more evident in women with larger cysts, more than one cyst, and greater responsiveness to ovarian hyperstimulation. Kumbak et al. (2008) investigated whether the space-occupying effect of a 10–50 mm endometrioma, rather than endometriosis, in 85 normal responder patients affected IVF results; 83 normal responder women with 10–35 mm simple ovarian cysts were used as the control group. Fewer oocytes were retrieved in patients with an endometrioma. The grade I embryo ratio and implantation rate were better in the simple ovarian cyst group. The presence of an endometriotic cyst during the IVF cycle was associated with lower embryo quality and a lower implantation rate; however, the pregnancy success rate was unaffected. This adverse effect may be due to the disease and not the presence of a cystic mass. Whether endometrioma excision has a positive or negative effect on IVF success rates has been debated. Garcia Velasco et al. (2004) did not observe a significant difference between the pregnancy rates of 133 women who underwent surgery for endometriomas before IVF (25.4%) and those of 56 subjects who underwent IVF without prior endometrioma removal (22.7%). However, the study was controversial because the diagnosis of an endometrioma in the control group was based on ultrasonography, and they were unable to remove all of the endometriomas due to surgical difficulties. The first RCT to investigate whether endometrioma removal affected subsequent IVF-ICSI cycles was conducted by Demirol et al. (2006). The authors prospectively randomised 99 patients into the following groups: group I (49 patients) underwent conservative ovarian surgery before an ICSI cycle and group II (50 patients) only underwent an ICSI cycle. No significant differences were observed between groups I and II in the fertilisation rate (86% vs 82%), the implantation rate (16.5% vs 18.5%) and the pregnancy rate (34% vs 38%). Because favourable IVF results cannot be obtained from the excision of endometriomas and the risk of decreased ovarian reserves is high with this procedure, a pertinent question is whether we should operate on endometriomas to improve fertility treatment results. The failure to detect an occult early stage malignancy is a rare but important concern (Ness 2003; Van Gorp et al. 2004). The two largest available studies regarding the risk of occult malignancy in endometriotic samples reported frequencies of 0.8% and 0.9% (Mostoufizadeh and Scully 1980; Stern et al. 2001). During ovarian stimulation and/or oocyte collection, endometriomas may rupture and, consequently, cause pelvic infection. The contamination of follicles with endometrioma material due to puncture or rupture is another risk factor of endometriomas. In patients with minimal and mild endometriosis, laparoscopic resection–ablation of endometriosis focal points or adhesions may enhance fecundity in the follow-up period and may improve the outcome of subsequent IVF/ICSI treatment in infertile women (Jacobson et al. 2010; Opøien et al. 2011). If an ovarian endometrioma 4 cm in diameter is present, laparoscopic ovarian cystectomy is recommended to histologically confirm the diagnosis, reduce the risk of infection, improve access to follicles and possibly improve ovarian responses (Kennedy et al. 2005). For infertile women with stage III/IV endometriosis who had previously undergone one or more operations, IVF-ET is a better therapeutic option than another operation for infertility
4
H. Hassa & Y. Aydin
(Practice Committee of the American Society for Reproductive Medicine 2006).
J Obstet Gynaecol Downloaded from informahealthcare.com by V U L Periodicals Rec on 10/04/14 For personal use only.
Laparoscopy after failed ART treatment To the best of our knowledge, no RCTs have evaluated the effect of diagnostic laparoscopy after failed ovulation induction, failed ovarian stimulation IUI or failed ART cycles. In a retrospective study by Ochoa Capelo et al. (2003), diagnostic laparoscopy was performed on 92 patients after four failed cycles of ovulation induction treatment with clomiphene citrate (CC). The laparoscopic findings were normal in only 36% of the cases, whereas endometriosis and/or pelvic adhesions were observed in 50% and 33% of the cases, respectively. Ochoa Capelo et al. (2003) concluded that laparoscopy is a useful tool in the work-up of an infertile couple but did not lead to a significant increase in pregnancy rates following laparoscopic surgery. An important finding regarding the role of laparoscopic evaluation and management after failed IVF cycles was obtained in a retrospective study by Littman et al. (2005). A total of 29 patients who had a mean of 2.2 failed IVF cycles underwent laparoscopic evaluation. The patients who elected not to undergo a laparoscopic procedure were assigned to the control group (35 patients). After the laparoscopic evaluation, 22 cases (76%) conceived, of which 13 conceived spontaneously. Of the patients who were diagnosed with stage I disease, 100% conceived. Overall, 83% of the patients with stage II disease conceived, 83% of the patients with stage III disease conceived and 62% of those with stage IV disease conceived. With the advancement of ART, clinicians are preferentially selecting a new controlled ovarian hyperstimulation/IVF-ICSI cycle after failed ART treatment. It is likely that at least 50% of patient pathologies, such as endometriosis or adhesions, can be detected if laparoscopy is performed after failed IVF treatment; however, no RCTs have confirmed this rate.
Periadnexal adhesions and surgery Pelvic adhesions that result from pelvic infections, endometriosis and previous surgeries may have a role in subfertility (Pabuccu and Gomel 2010). Pelvic adhesions can contribute to tubal dysfunction even if HSG is normal. Periadnexal adhesions may be the sole causative factor for infertility, which encapsulate the fimbriae portion of the patent tube and prevent the oocyte from being captured by otherwise normal fimbria. In addition, periovarian adhesions may adversely affect follicular development (Gomel and McComb 2010). In a controlled case study with a 24-month follow-up, Tulandi and co-workers (1990) demonstrated that adhesiolysis increased pregnancy rates. They compared 69 women who had periadnexal adhesions that were discovered during laparoscopic examination, which were consequently treated with salpingo-ovariolysis by laparotomy, with 78 women who had the same extent of adhesions and who were not treated. They found that the cumulative pregnancy rates at the 12- and 24-month follow-up were 32% and 45% in the treated group and 11% and 16% in the untreated group, respectively. They concluded that treatment with salpingo-ovariolysis is associated with a higher pregnancy rate. Gomel (1983) reported the effect of laparoscopic salpingo-ovariolysis in 92 patients. The duration of infertility was longer than 20 months for all of the patients. In 79 cases, the periadnexal adhesions were severe, and all of these patients were followed-up for at least 9 months. Of the total 92 patients, 57 (62%) achieved at least one intrauterine pregnancy, 54 (58.7%) had one or more full-term pregnancies and five (5.4%) had ectopic pregnancies. Gomel concluded that in a selected patient population and when performed by well-trained operators, laparoscopic salpingo-ovariolysis is a
low-risk procedure that is associated with good spontaneous conception rates and intrauterine pregnancies. In a subsequent RCT by Gurgan et al. (1992), 40 clomiphene citrate-resistant PCOS patients underwent laparoscopic laser photocoagulation of the ovaries and were randomly assigned to either undergo second-look laparoscopy with lysis of adhesions within 3–4 weeks of the initial laparoscopy (n 19) or expectant management (n 20). The pregnancy rates over 6 months were similar in the two groups. The authors concluded that the spontaneous conception rates did not increase during the short time period of 6 months following laparoscopic adhesiolysis. In a 2010 Cochrane review, Duffy et al. (2009) reported on the effect of second-look laparoscopy and adhesiolysis following pelvic reproductive surgery. They found that the odds of pregnancy (OR 0.96, 95% CI, 0.44–2.07) or live birth (OR 0.67, 95% CI, 0.19–2.32) were not significantly different between second-look laparoscopy plus adhesiolysis and no second-look laparoscopy. Pelvic adhesions around the ovaries may interrupt the blood supply to the ovaries, thereby resulting in impaired gonadotropin access to target organs (Nagata et al. 1998). In addition, adhesions may lead to impaired access to the ovary during oocyte pick-up, which results in a decreased number of collected oocytes (Daniell et al. 1983). In contrast, an important treatment for adhesions is a surgical technique known as adhesiolysis. Salpingo-ovariolysis should be performed using the microsurgery principles defined by Gomel (2003, 2010). Facets of microsurgery include: using magnification; employing a technique to minimise tissue injury; preventing foreign body contamination; obtaining meticulous pinpoint haemostasis; identifying proper cleavage planes; completely excising abnormal tissues; precisely aligning and approximating tissue planes and performing a thorough pelvic lavage at the end of the procedure. Using ideal surgical techniques, we can obtain acceptable spontaneous conception rates following salpingo-ovariolysis. However, there is insufficient evidence to recommend performing second-look laparoscopies with adhesiolysis. New RCTs are needed to determine whether performing routine adhesiolysis can improve reproductive outcomes in infertile couples.
Hydrosalpinges Hydrosalpinges adversely affect reproductive outcomes and several factors have been implicated, including a mechanical interference with implantation and toxic effects on the endometrium and embryo (Beyler et al. 1997; Meyer et al. 1997). In 2010, a Cochrane review that included five RCTs with 646 patients examined the effects of interventions on hydrosalpinges before IVF (Johnson et al. 2010). The odds ratio for a clinical pregnancy after undergoing a salpingectomy compared with no surgical treatment was 2.40 (95% CI, 1.49–3.86). The odds ratio for a clinical pregnancy after undergoing a tubal occlusion compared with no surgical treatment was 4.66 (95% CI, 2.17–10.01). According to reproductive performance, neither surgical procedure was superior to the other (salpingectomy compared with occlusion). However, the effects of the procedure were predominant in the ultrasound-visible hydrosalpinx, particularly if the procedure was bilateral (Strandell et al. 1999). Other treatment strategies, such as ultrasound-guided aspiration of hydrosalpingeal fluid at the time of oocyte retrieval, have been suggested as alternative treatments (Van Voorhis et al. 1998) but their effectiveness has not been established and evidence suggests that the fluid reaccumulates rapidly (Bloechle et al. 1997). The negative effects of hydrosalpinges on spontaneous conceptions and IVF pregnancies are well established (Beyler et al. 1997; Meyer et al. 1997). However, with the substantial progress
Laparoscopy in infertility
J Obstet Gynaecol Downloaded from informahealthcare.com by V U L Periodicals Rec on 10/04/14 For personal use only.
in ART, there has been a significant decline in the practice of reconstructive tubal surgery in the form of salpingostomy with a hydrosalpinx indication. Salpingostomy, or salpingoneostomy, is the creation of a new stoma in the fallopian tube with the hydrosalpinx (Gomel 2010). Periadnexal adhesions generally accompany the hydrosalpinx; therefore, the most important predictors of treatment success subsequent to salpingostomy are the degree of pre-existing tubal damage and the extent of periadnexal adhesion. Therefore, salpingo-ovariolysis needs to be completed before a salpingostomy can be performed. Factors that affect the outcome of a salpingostomy include the distal tubal ampulla diameter, the tubal wall thickness, the nature of the tubal endothelium and the extent and type of periadnexal adhesions (Gomel 2003). Reported live birth rates following microsurgical salpingostomy range from 17% to 37% (Gomel 2010). Therefore, in selected cases with tubal factor infertility, laparoscopic salpingostomy may be indicated, which offers the advantage of natural conception.
Laparoscopic ovarian diathermy in PCOS patients The initial steps to improve ovulation in ovulatory PCOS patients include lifestyle modifications, such as weight reduction in overweight patients with dietary restriction and exercise. The next conventional approach is ovulation induction with CC (Gomel and Yarali 2004). Approximately 20% of infertile patients with PCOS will not ovulate on CC. After ovulation failure has been demonstrated with this treatment, clinicians must select the best treatment option for ovulation induction. Ovulation induction with gonadotropins results in high multiple pregnancy rates, up to 25%, and an increased risk of OHSS (Guzick et al. 1999). Another option for treating women with CC resistance (ovulation failure with CC) is laparoscopic ovarian diathermy (LOD), which is an alternative ovarian wedge resection method. However, this method is more invasive and damaging. The common procedure for LOD includes making four punctures per ovary by applying a diathermy current with a specially designed ovarian diathermy needle (Armar et al. 1990; Li et al. 1998). There are various hypotheses regarding the mechanism of action, such as nonspecific stromal destruction or the opening of follicular capsules that release follicular fluid, which contains androgens, thereby removing the ovulation block (Cohen et al. 1972; Gjönnaess 1984). A significant reduction in serum androgen levels, an increase in FSH levels and a decrease in LH pulse amplitude have been observed, independent of the mechanism (Campo 1998). A rapid response following LOD has been reported, such as ovulation within 2–4 weeks and menstruation within 4–6 weeks. In a large RCT, Bayram et al. (2004) reported an ovulation rate of 70% per cycle, a cumulative conception rate of 76% and a live birth rate of 64% following LOD in PCOS patients. Recently, Youssef and Atallah (2007) compared unilateral and bilateral ovarian drilling in 87 patients with PCOS in an RCT and found that the ovulation, pregnancy and miscarriage rates were similar in both groups. Therefore, unilateral drilling is as successful as bilateral drilling but less time-consuming. As clinicians, we must remember that LOD is a surgical procedure. In addition to the general surgical and anaesthetic complications, the most detrimental complications for an infertile couple are pelvic/ovarian adhesions and premature ovarian failure. Mercorio et al. (2008) studied the factors that affect adhesion formation in an RCT. A total of 96 women were randomised into two study groups of 48 women each: one group was treated with six punctures on the left ovary and 12 on the right ovary, and the other group was treated with six punctures on the right ovary and 12 on the left ovary. Using short-term second-look laparoscopy, adhesion formation was detected in 60% of women and in 46% of ovaries.
5
Dense adhesions were more likely to be found on the left ovary, regardless of the number of ovarian punctures performed. Therefore, in LOD cases, we should preferentially select the right ovary for diathermy. Api (2009) investigated whether LOD is harmful to ovarian reserve markers and concluded that there was no evidence of decreased ovarian reserve or premature ovarian failure (POF) associated with LOD in women with PCOS. Most of the changes in the ovarian reserve markers that were observed after LOD could be interpreted as a normalisation of ovarian function rather than a reduction in ovarian reserve. Weerakiet et al. (2007) evaluated ovarian reserve using hormones and ultrasonography in 21 women with PCOS who underwent LOD and compared them with PCOS patients who did not undergo LOD and with normal ovulatory women. The PCOS women who underwent LOD and the PCOS women who did not undergo LOD had a significantly greater ovarian reserve than the age-matched controls. Clinical studies have investigated whether there are any differences between treatment with gonadotropins and LOD. Farquhar et al. (2007) reported that there were no differences in the live birth and clinical pregnancy rates between LOD and gonadotropins and the ORs were 1.04 (95% CI 0.59–1.85) and 1.08 (95% CI 0.69–1.71), respectively. The multiple pregnancy rates were lower with ovarian drilling than with gonadotropins (1% compared with 16%; OR 0.13, 95% CI, 0.03–0.52). There were no differences in the miscarriage rates between the two groups (OR 0.81, 95% CI, 0.36–1.86). In addition, Palomba et al. (2009) concluded that in CC-resistant PCOS patients, LOD should be considered before administering gonadotropins. Within the limits of strict surgical principles, LOD is a better option than ovulation induction with gonadotropins in CCresistant PCOS patients. A major advantage of LOD is a decreased risk of multiple pregnancies. LOD generally results in unifollicular ovulation and does not require intensive follicular monitoring (Thessaloniki ESHRE/ASRM-sponsored PCOS Consensus Workshop Group 2008).
Conclusion Laparoscopy is not a routine part of the diagnostic approach for infertile couples. Every patient and clinical condition must be assessed individually. Regarding tubal occlusion, laparoscopy is recommended when HSG reveals a bilateral obstruction. Laparoscopy can be postponed until at least 10 months after a normal patency or unilateral obstruction is revealed by HSG, particularly in females 36 years of age with normal ovarian reserves. In patients with a history of tuberculosis or severe pelvic infection, laparoscopy should be considered as a first-step approach instead of HSG because in these clinical conditions, tubal morphology and fimbria functional capacity are more important than demonstrating tubal patency. Further randomised controlled trials are warranted to determine whether laparoscopy with IUI should be performed and whether this procedure should be performed before or after IUI. Clinicians should consider the option of diagnostic laparoscopy before IUI in patients with a history of pelvic infection, ectopic pregnancy, tubal surgery or symptoms of endometriosis. In patients with minimal and mild endometriosis, laparoscopic resection–ablation of endometriosis focal points or adhesions may enhance fecundity in the follow-up period and may improve the outcome of subsequent IVF/ICSI treatment in infertile women. If an ovarian endometrioma 4 cm in diameter is present, laparoscopic ovarian cystectomy is recommended to histologically confirm the diagnosis, reduce the risk of infection, improve access
J Obstet Gynaecol Downloaded from informahealthcare.com by V U L Periodicals Rec on 10/04/14 For personal use only.
6
H. Hassa & Y. Aydin
to follicles and possibly improve ovarian response. For infertile women who have stage III/IV endometriosis and who have previously had one or more operations for infertility, IVF-ET is a better therapeutic option than another operation for infertility. No RCTs have evaluated the effects of diagnostic laparoscopy after failed ovulation induction, failed ovarian stimulation IUI or failed ART cycles; however, at least 50% of patient pathologies, such as endometriosis or adhesions, can be detected if laparoscopy is performed. In addition, no evidence suggests that laparoscopy with adhesiolysis before ART increases the pregnancy rate in ART cycles. A hydrosalpinx negatively affects reproductive outcomes. Laparoscopic salpingectomy is indicated in the case of an ultrasound-visible hydrosalpinx. The effect of laparoscopic surgery is more predominant in the presence of a bilateral hydrosalpinx. In selected cases with tubal factor infertility, laparoscopic salpingostomy may be indicated, which offers the advantage of natural conception. LOD is an alternative treatment method to ovulation induction with gonadotropins in patients with CC-resistant PCOS and generally results in unifollicular ovulation. Additionally, LOD allows us to preclude multiple pregnancies and intensive follicular monitoring. Considering the advantages of a low cost, beneficial long-term hormonal effects, a decreased multiple pregnancy risk and the same pregnancy rates as treatment with gonadotropins, we should consider the LOD option in patients with CC-resistant PCOS. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References Adamson GD, Pasta DJ. 1994. Surgical treatment of endometriosis-associated infertility: meta-analysis compared with survival analysis. American Journal of Obstetrics and Gynecology 171:1488–1504. Api M. 2009. Is ovarian reserve diminished after laparoscopic ovarian drilling? Gynecological Endocrinology 25:159–165. Armar NA, McGarrigle HH, Honour J, Holownia P, Jacobs HS, Lachelin GC. 1990. Laparoscopic ovarian diathermy in the management of anovulatory infertility in women with polycystic ovaries: endocrine changes and clinical outcome. Fertility and Sterility 53:45–49. Bayram N, van Wely M, Kaaijk EM, Bossuyt PM, van der Veen F. 2004. Using an electrocautery strategy or recombinant follicle stimulating hormone to induce ovulation in polycystic ovary syndrome: randomised controlled trial. British Medical Journal 328:192. Beyler SA, James KP, Fritz MA, Meyer WR. 1997. Hydrosalpingeal fluid inhibits in-vitro embryonic development in a murine model. Human Reproduction 12:2724–2728. Bloechle M, Schreiner T, Lisse K. 1997. Recurrence of hydrosalpinges after transvaginal aspiration of tubal fluid in an IVF cycle with development of a serometra. Human Reproduction 12:703–705. Bosteels J, Van Herendael B, Weyers S, D’Hooghe T. 2007. The position of diagnostic laparoscopy in current fertility practice. Human Reproduction Update 13:477–485. Busacca M, Olive DL. 2010. Treatment of endometriosis associated infertility. In: Gomel V, Brill AI, editors. Reconstructive and reproductive surgery in gynecology. London: Informa Healthcare. p 84–96. Campo S. 1998. Ovulatory cycles, pregnancy outcome and complications after surgical treatment of polycystic ovary syndrome. Obstetrical and Gynecological Survey 53:297–308. Cohen J, Audebert A, de Brux J, Giorgi H. 1972. Sterility due to dysovulation: prognostic and therapeutic role of ovarian biopsy during calioscopy. Journal de Gynécologie, Obstétrique, et Biologie de la Reproduction 1:657–671. Crosignani PG, Rubin BL; The ESHRE Capri Workshop Group. 2000. Optimal use infertility diagnostic tests and treatments. Human Reproduction 15:723–732. Daniell JF, Pittaway DE, Maxson WS. 1983. The role of laparoscopic adhesiolysis in an in vitro fertilization program. Fertility and Sterility 40:49–52.
Deaton JL, Gibson M, Blackmer KM, Nakajima ST, Badger GJ, Brumsted JR. 1990. A randomised, controlled trial of clomiphene citrate and intrauterine insemination in couples with unexplained infertility or surgically corrected endometriosis. Fertility and Sterility 54:1083–1087. Demirol A, Guven S, Baykal C, Gurgan T. 2006. Effect of endometrioma cystectomy on IVF outcome: a prospective randomized study. Reproductive Biomedicine Online 12:639–643. Donnez J, Nisolle M, Gillet N, Smets M, Bassil S, Casanas-Roux F. 1996. Large ovarian endometriomas. Human Reproduction 11:641–646. Duffy JM, Johnson N, Ahmad G, Watson A. 2009. Postoperative procedures for improving fertility following pelvic reproductive surgery. Cochrane Database of Systematic Reviews (2):CD001897. Evers JL, Land JA, Mol BW. 2003. Evidence-based medicine for diagnostic questions. Seminars in Reproductive Medicine 21:9–15. Farquhar C, Lilford R, Marjoribanks J, Vanderkerchove P. 2007. Laparoscopic drilling by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database of Systematic Reviews (3):CD001122. Garcia-Velasco JA, Mahutte NG, Corona J, Zuniga V, Giles J, Pellicer A. 2004. Removal of endometriomas before in vitro fertilization does not improve fertility outcomes: a matched, case-control study. Fertility and Sterility 81:1194–1206. Gjönnaess H. 1984. Polycystic ovarian syndrome treated by ovarian electrocautery through the laparoscope. Fertility and Sterility 41:20–25. Gomel V, McComb PF. 2010. Investigation of tubal and peritoneal causes of infertility. In: Gomel V, Brill AI, editors. Reconstructive and reproductive surgery in gynecology. 1st ed. London: Informa Healthcare. p 243–259. Gomel V, Taylor PJ. 1995. Diagnostic and operative gynecologic laparoscopy. St Louis: Mosby. p 99–113. Gomel V, Yarali H. 2004. Surgical treatment of polycystic ovary syndrome associated with infertility. Reproductive Biomedicine Online 9:35–42. Gomel V. 1983. Salpingo-ovariolysis by laparoscopy in infertility. Fertility and Sterility 40:607–611. Gomel V. 2003. Reconstructive tubal surgery. In: Rock JA, Jones HW, editors. Te Linde’s operative gynecology. 9th ed. Philadelphia: Lippincott Williams and Wilkins. p 557–595. Gomel V. 2010. Reproductive surgery. In: Gomel V, Brill AI, editors. Reconstructive and reproductive surgery in gynecology. London: Informa Healthcare. p 259–281. Gurgan T, Urman B, Aksu T, Yarali H, Develioglu O, Kisnisci H. 1992. The effect of short interval laparoscopic lysis of adhesions on pregnancy rates following Nd-YAG laser photocoagulation of polycystic ovaries. Obstetrics and Gynecology 80:45–47. Guzick DS, Carson SA, Coutifaris C, Overstreet JW, Factor-Litvak P, Steinkampf MP et al. 1999. Efficacy of superovulation and intrauterine insemination in the treatment of infertility. New England Journal of Medicine 340:177–183. Jacobson TZ, Duffy JM, Barlow D, Farquhar C, Koninekx PR, Olive D. 2010. Laparoscopic surgery for subfertility associated with endometriosis. Cochrane Database of Systematic Reviews (1):CD001398. Johnson N, van Voorst S, Sowter MC, Strandell A, Mol BW. 2010. Surgical treatment for tubal disease in women due to undergo in vitro fertilisation. Cochrane Database of Systematic Reviews (1):CD002125. Kennedy S, Bergqvist A, Chapron C, D’Hooghe T, Dunselman G, Greb R et al.; ESHRE Special Interest Group for Endometriosis Endometrium Guideline Development Group. 2005. ESHRE guideline for the diagnosis and treatment of endometriosis. Human Reproduction 20:2698–2704. Kumbak B, Kahraman S, Karlikaya G, Lacin S, Guney A. 2008. In vitro fertilization in normoresponder patients with endometriomas: comparison with basal simple ovarian cysts. Gynecologic and Obstetric Investigation 65:212–216. Li TC, Saravelos H, Chow MS, Chisabingo R, Cooke ID. 1998. Factors affecting the outcome of laparoscopic ovarian drilling for polycystic ovarian syndrome in women with anovulatory infertility. British Journal of Obstetrics and Gynaecology 105:338–344. Littman E, Giudice L, Lathi R, Berker B, Milki A, Nezhat C. 2005. Role of laparoscopic treatment of endometriosis in patients with failed in vitro fertilization cycles. Fertility and Sterility 84:1574–1508. Maas JW, Evers JL, ter Riet G, Kessels AG. 1997. Pregnancy rate following normal versus abnormal hysterosalpingography findings: a meta-analysis. Gynecologic and Obstetric Investigation 443:79–83. Marcoux S, Maheux R , Berube S. 1997. Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis. New England Journal of Medicine 3337:217–222. Mercorio F, Mercorio A, Di Spiezio Sardo A, Barba GV, Pellicano M, Nappi C. 2008. Evaluation of ovarian adhesion formation after laparoscopic ovarian drilling by second-look minilaparoscopy. Fertility and Sterility 89:1229–1233.
J Obstet Gynaecol Downloaded from informahealthcare.com by V U L Periodicals Rec on 10/04/14 For personal use only.
Laparoscopy in infertility Meyer WR, Castelbaum AJ, Somkuti S, Sagoskin AW, Doyle M, Harris JE et al. 1997. Hydrosalpinges adversely affect markers of endometrial receptivity. Human Reproduction 12:1393–1398. Mol BW, Collins JA, Burrows EA, van der Veen F, Bossuyt PM. 1999. Comparison of hysterosalpingography and laparoscopy in predicting fertility outcome. Human Reproduction 114:1237–1242. Mostoufizadeh M, Scully RE. 1980. Malignant tumors arising in endometriosis. Clinical Obstetrics and Gynecology 23:951–963. Nagata Y, Honjou K, Sonoda M, Makino I, Tamura R, Kawarabayashi T. 1998. Peri-ovarian adhesions interfere with the diffusion of gonadotrophin into the follicular fluid. Human Reproduction 13:2072–2076. Ness RB. 2003. Endometriosis and ovarian cancer: thoughts on shared pathophysiology. American Journal of Obstetrics and Gynecology 189: 280–294. Nuoja-Huttunen S, Tomas C, Bloigu R, Tuomivaara L, Martikainen H. 1999. Intrauterine insemination treatment in subfertility: an analysis of factors affecting outcome. Human Reproduction 14:698–703. Ochoa Capelo F, Kumar A, Steinkampf MP, Azziz R. 2003. Laparoscopic evaluation following failure to achieve pregnancy after ovulation induction with clomiphene citrate. Fertility and Sterility 80:1450–1453. Omland AK, Tanbo T, Dale PO, Abyholm TA. 1998. Artificial insemination by husband in unexplained infertility compared with infertility associated with peritoneal endometriosis. Human Reproduction 13:2602–2605. Opøien HK, Fedorcsak P, Byholm T, Tanbo T. 2011. Complete surgical removal of minimal and mild endometriosis improves outcome of subsequent IVF/ ICSI treatment. Reproductive Biomedicine Online 23:389–395. Pabuccu R, Gomel V. 2010. General principles in preservation of fertility in gynecologic surgery. In: Gomel V, Brill AI, editors. Reconstructive and reproductive surgery in gynecology. 1st ed. London: Informa Healthcare. p 281–285. Palomba S, Falbo A, Zullo F. 2009. Management strategies for ovulation induction in women with polycystic ovary syndrome and known clomifene citrate resistance. Current Opinion in Obstetrics and Gynecology 21:465–473. Parazzini F. 1999. Ablation of lesions or no treatment in minimal-mild endometriosis in infertile women: a randomized trial. Gruppo Italiano per lo Studio dell’Endometriosi. Human Reproduction 14:1332–1334. Practice Committee of the American Society for Reproductive Medicine. 2006. Endometriosis and infertility. Fertility and Sterility 86:156–160. Rowe PJ, Comhaire FH, Hargreave TB, Mahmoud AMA. 1993. WHO manual for the standardized investigation of the infertile couple. Cambridge: Cambridge University Press. Somigliana E, Infantino M, Benedetti F, Arnoldi M, Calanna G, Ragni G. 2006a. The presence of ovarian endometriomas is associated with a reduced responsiveness to gonadotropins. Fertility and Sterility 86:192–196. Somigliana E, Vercellini P, Vigano P, Ragni G, Crosignani PG. 2006b. Should endometriomas be treated before IVF-ICSI cycles? Human Reproduction Update 12:57–64. Speroff L, Fritz MA, editors. 2011. Clinical gynecologic endocrinology and infertility. 8th ed. Philadelphia: Lippincott, Williams and Wilkins. p 1137–1191. Stern RC, Dash R, Bentley RC, Snyder MJ, Haney AF, Robboy SJ. 2001. Malignancy in endometriosis: frequency and comparison of ovarian and
7
extraovarian types. International Journal of Gynecological Pathology 20:133–139. Strandell A, Lindhard A, Waldenstrom U, Thorburn J, Janson PO, Hamberger L. 1999. Hydrosalpinx and IVF outcome: a prospective, randomized multicentre trial in Scandinavia on salpingectomy prior to IVF. Human Reproduction 14:2762–2769. Strathy JH, Molgaard CA, Coulam CB, Melton LJ 3rd. 1982. Endometriosis and infertility: a laparoscopic study of endometriosis among fertile and infertile women. Fertility and Sterility 38:667–672. Swart P, Mol BW, van der Veen F, van Beurden M, Redekop WK, Bossuyt PM. 1995. The accuracy of hysterosalpingography in the diagnosis of tubal pathology: a meta-analysis. Fertility and Sterility 64:486–491. Tanahatoe SJ, Hompes PGA, Lambalk CB. 2003. Accuracy of diagnostic laparoscopy in the infertility work-up before intrauterine insemination. Fertility and Sterility 79:361–366. Tanahatoe SJ, Lambalk CB, Hompes PGA. 2005. The role of laparoscopy in intrauterine insemination: a prospective randomized reallocation study. Human Reproduction 20:3225–3230. Templeton A, Morris JK, Parslow W. 1996. Factors that affect outcome of in-vitro fertilisation treatment. Lancet 348:1402–1406. Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. 2008. Consensus on infertility treatment related to polycystic ovary syndrome. Human Reproduction 23:462–477. Tulandi T, Collins JA, Burrows E, Jarrell JF, McInnes RA, Wrixon W et al. 1990. Treatment-dependent and treatment-independent pregnancy among women with periadnexal adhesions. American Journal of Obstetrics and Gynecology 162:354–357. Tummon IS, Asher LJ, Martin JSB, Tulandi T. 1997. Randomized controlled trial of superovulation and insemination for infertility with minimal or mild endometriosis. Fertility and Sterility 68:8–12. Van Gorp T, Amant F, Neven P, Vergote I and Moerman P. 2004. Endometriosis and the development of malignant tumours of the pelvis. A review of literature. Best Practice and Research. Clinical Obstetrics and Gynaecology 18:349–371. Van Kooij RJ, Looman CW, Habbema JD, Dorland M, te Velde ER. 1996. Age dependent decrease in embryo implantation rate after in vitro fertilization. Fertility and Sterility 66:769–775. Van Voorhis BJ, Sparks AE, Syrop CH, Stovall DW. 1998. Ultrasound guided aspiration of hydrosalpinges is associated with improved pregnancy and implantation rates after in-vitro fertilization cycles. Human Reproduction 13:736–739. Weerakiet S, Lertvikool S, Tingthanatikul Y, Wansumrith S, Leelaphiwat S, Jultanmas R. 2007. Ovarian reserve in women with polycystic ovary syndrome who underwent laparoscopic ovarian drilling. Gynecological Endocrinology 23:455–460. Wordsworth S, Buchanan J, Mollison J, Harrild K, Robertson L, Tay C et al. 2011. Clomifene citrate and intrauterine insemination as first-line treatments for unexplained infertility: are they cost-effective? Human Reproduction 26:369–375. Youssef H, Atallah MM. 2007. Unilateral ovarian drilling in polycystic ovarian syndrome: a prospective randomized study. Reproductive Biomedicine Online 15:457–462.
REVIEW
The role of laparoscopy in the management of infertility H. Hassa & Y. Aydin
J Obstet Gynaecol Downloaded from informahealthcare.com by V U L Periodicals Rec on 10/04/14 For personal use only.
Reproductive Medicine Unit, Department of Obstetrics and Gynaecology, Eskisehir Osmangazi University Medical Faculty, Eskisehir, Turkey
The advancement of new perspectives in assisted reproductive technology (ART) through the use of modern infertility evaluation techniques has led clinicians to reassess how infertility should best be treated. The usefulness of laparoscopy in the diagnostic work-up of infertile patients or in patients who are unresponsive to fertility treatments is debatable. The purpose of this review is to define the role of laparoscopy in the management of infertility, which is one of the most controversial aspects of reproductive medicine. To the best of our knowledge, laparoscopy is currently not a routine step in the evaluation of infertile women; every patient and clinical condition must be assessed individually. In this review, we investigated the effectiveness and the utility of laparoscopy as a diagnostic and therapeutic tool in the management of infertility. Various topics and parameters in ART will be discussed based on the evidence that is currently available. Keywords: Assisted reproductive technology, fertility, laparoscopy
Introduction In the 1990s, laparoscopy was the final step in the routine diagnostic approach for the evaluation of infertile couples (Rowe et al. 1993). However, due to the advancement of new perspectives in assisted reproductive technology (ART), the process of evaluating infertile couples has changed. Currently, the most widely accepted approach to infertility is no longer based on diagnosing an exact aetiology. The scope and the sequence of modern infertility evaluation focus on the most efficient and cost-effective tests. The investigation of infertile couples should be rapid and inexpensive, using minimally invasive tests (Gomel and McComb 2010). In addition, the focus of treatment for infertility has shifted from the systematic correction of each identified factor to applying the most efficient therapy, which may be ART (Speroff and Fritz 2011). The most common initial diagnostic tests for the evaluation of an infertile couple are the mid-luteal phase progesterone assay; a test for tubal patency, such as hysterosalpingography (HSG) for females and semen analysis for males. Laparoscopy is reserved for further diagnosis or may be used in combination with endoscopic surgery (Crosignani and Rubin 2000). Therefore, ART may be performed on suboptimally investigated couples. In cases of treatment failure or ART failure, secondary invasive diagnostic approaches, such as laparoscopy, are typically performed. The most important advantages of a limited evaluation of infertile couples, which excludes laparoscopy in the diagnostic work-up, are the prevention of a delay in treatment and minimal initial testing. However, a disadvantage of this approach is that
abnormalities that are associated with subfertility can be overlooked. In-vitro fertilisation (IVF) clinicians generally discount diagnostic laparoscopy (Bosteels et al. 2007). The aim of this review is to describe recent changes in the use of laparoscopy for diagnostic and therapeutic purposes in the treatment of infertility and specify the clinical conditions under which laparoscopy may be safely used as a diagnostic test in infertile couples. The effectiveness and the utility of laparoscopy will be discussed in various ART topics and parameters, based on the evidence that is currently available. In general, diagnostic laparoscopy may be used for otherwise unexplained infertility in the following circumstances: • To demonstrate tubal patency • To determine treatment before intrauterine insemination (IUI) or after IUI cycle failure. However, laparoscopy may be performed for diagnostic purposes and with therapies for fertility, in infertile couples who have any of the following conditions: • • • • •
Endometriosis After failed IVF Significant pelvic adhesions Hydrosalpinges Polycystic ovarian syndrome (PCOS).
Tubal patency HSG is the most widely used test for the evaluation of infertile couples to determine tubal patency. HSG can be used to test tubal patency and for a morphological evaluation of the tubes and uterus. In addition to normal morphological findings, HSG can detect tubal occlusion, lesions (salpingitis isthmica nodosa or endometriosis) and intratubal architecture (dilatation, rugae and intratubal adhesions) (Gomel 2010; Gomel and Taylor 1995). For detecting tubal patency, HSG has a moderate sensitivity of 65% and a relatively high specificity of 83% (Evers et al. 2003; Swart et al. 1995). The clinical implications of an obstruction that is detected by HSG, include a high probability that the tube is open (approximately 60%); however, when HSG shows patency, there is a low probability that the tube is occluded (approximately 5%). Generally, the rate of treatment-independent pregnancy is highest when both tubes are patent, according to HSG (Speroff and Fritz 2011). However, laparoscopy provides a general view of the pelvic organs and any bowel and/or pelvic peritoneal adhesions; therefore, this procedure may be used to identify milder forms of distal
Correspondence: Y. Aydin, Reproductive Medicine Unit, Department of Obstetrics and Gynaecology, Eskisehir Osmangazi University Medical Faculty, Eskisehir, 26000, Turkey. E-mail: [email protected]
J Obstet Gynaecol Downloaded from informahealthcare.com by V U L Periodicals Rec on 10/04/14 For personal use only.
2
H. Hassa & Y. Aydin
tubal occlusive diseases, such as fimbrial agglutination or fimbrial phimosis. In addition, we can detect minimal and mild endometriosis, which may not be detected on pelvic ultrasonography (USG) or HSG. Most importantly, at the time of diagnosis, diseases may be treated laparoscopically. In pelvic adhesive diseases, which are caused by pathological factors (endometriosis or pelvic infection), tubal patency can be demonstrated by the passage of contrast media using HSG; however, tubal fimbriae function, which primarily determines fertility, cannot be properly demonstrated. In addition to tubal patency, tubal functions, such as free fimbrial movement, are necessary for ovum capture and fertilisation. Even in the presence of open fallopian tubes, as detected by HSG, deficient fimbrial movement that is inadequate for ovum retrieval may cause infertility. Therefore, laparoscopy is an exceptional test that can determine fimbrial function in addition to the patency of tubes, which is vital for ovum retrieval (Speroff and Fritz 2011). Using laparoscopy, the prognosis of patients is best when both fallopian tubes are patent, poor when both tubes are blocked and intermediate when only one tube is open (Maas et al. 1997; Mol et al. 1999). When testing for tubal patency, false-negatives in HSG are more common than in laparoscopy. Consequently, tubal blockages detected by HSG are often false-positives; however, obstructions diagnosed by laparoscopy are most likely truepositives. Therefore, the prognosis of a tubal obstruction (unilateral and/or bilateral) is poorer when diagnosed with laparoscopy than with HSG (Speroff and Fritz 2011). In a large prospective cohort study, Mol et al. (1999) demonstrated that unilateral and bilateral tubal occlusion, as determined by HSG and laparoscopy, were associated with treatmentindependent pregnancy. After a normal or unilateral occlusion was detected by HSG, laparoscopy revealed a bilateral occlusion in 5% of patients, and the probability of fertility in these patients was zero. The likelihood of fertility in the cases with a bilateral occlusion according to HSG was significantly reduced when laparoscopy indicated a unilateral or bilateral occlusion. The authors recommended that laparoscopy be postponed until at least 10 months after normal or unilateral abnormal HSG, whereas laparoscopy provides useful information when performed immediately after bilateral abnormal HSG. However, when deciding whether to delay laparoscopy for 10 months, clinicians must consider other prognostic factors, particularly the age of the patient. In females 36 years of age, IVF success rates begin to decline; therefore, a delay in a diagnosis is not acceptable (Templeton et al. 1996; Van Kooij et al. 1996). Laparoscopy is recommended when HSG reveals a bilateral obstruction. This procedure can be postponed for at least 10 months after normal patency or a unilateral obstruction is revealed by HSG, especially in females 36 years of age. In contrast, if HSG indicates patency in one or both tubes and the patient has a history of pelvic infection, ectopic pregnancy, tubal surgery or symptoms of endometriosis, the patient should be offered laparoscopy. For patients with a history of tuberculosis or severe pelvic infection, laparoscopy should be considered as a first-step approach instead of HSG because in these clinical conditions, tubal morphology and fimbrial functional capacity are more important than demonstrating tubal patency.
The role of laparoscopy in IUI cycles IUI is generally the standard treatment option for unexplained infertility and mild male factor infertility. After the standard diagnostic work-up, which includes HSG, clinicians primarily treat these patients with expectant management or IUI controlled ovarian stimulation (Wordsworth et al. 2011). However, treatment
failure presents a dilemma: either continue with additional diagnostic procedures, such as laparoscopy, or proceed directly with ART. Clinicians typically encounter this quandary before IUI treatment failure. Current treatments, such as empirical clomiphene citrate and unstimulated IUI, are costly and do not lead to increased live birth rates compared with expectant management of unexplained infertility (Wordsworth et al. 2011). Tanahatoe et al. (2003) retrospectively analysed the role of diagnostic laparoscopy in the evaluation of infertility before IUI. They investigated the prevalence of laparoscopic findings that led to a change in treatment decisions before IUI in 495 patients with normal HSG. Laparoscopy revealed pathological abnormalities, such as endometriosis and adhesions, in 35% of the patients and the initial treatment decisions were changed in 25% of the patients. Overall, 21% of the patients had laparoscopic abnormalities that were treated directly during laparoscopy, followed by IUI treatment. Additionally, 4% of patients had severe pathologies and IVF or secondary surgery was recommended. In a randomised controlled trial, Tanahatoe et al. (2005) compared the accuracy of standard laparoscopy before IUI with laparoscopy that was performed after six unsuccessful cycles of IUI. A total of 154 patients were equally randomised into a diagnostic laparoscopy first (DLSF) group or an IUI first (IUIF) group. Abnormal findings detected during laparoscopy (adhesiolysis, vaporisation of endometriosis, and fimbriolysis), which required treatment, were comparable in the DLSF and IUIF groups (48% compared with 56%; p 0.63; OR 1.4; 95% CI 0.5–3.6). The on-going pregnancy rate in the DLSF group was 44% compared with 49% in the IUIF group (p 0.63; OR 1.2; 95% CI 0.7–2.3). There were three major endpoints from this study. First, performing laparoscopy before IUI did not increase the on-going pregnancy rate. Second, the number of abnormalities that required laparoscopic intervention was not significantly higher in the group who underwent laparoscopy after 6 cycles of IUI compared with the group who underwent immediate laparoscopy before IUI. Third, 48% of the DLSF group and 56% of the IUIF group had abnormal findings during laparoscopy that resulted in a laparoscopic intervention. These rates were higher than a previously detected total abnormality rate of 35%. After combining live birth rates and on-going pregnancies after 20 weeks, a 2010 Cochrane meta-analysis demonstrated the superiority of laparoscopic surgery over diagnostic laparoscopy in the presence of minimal and mild endometriosis (Jacobson et al. 2010). The odds ratio (OR) was 1.64 (95% CI 1.05–2.57) in favour of laparoscopic surgery. Further randomised controlled trials are warranted to determine whether laparoscopy should be performed with IUI and whether this procedure should be performed before or after IUI. We believe that an indication for diagnostic laparoscopy before IUI should be confirmed in the presence of a history of pelvic infection, ectopic pregnancy, tubal surgery or symptoms of endometriosis.
The role of laparoscopy in endometriosis Endometriosis is significantly associated with infertility. The prevalence of endometriosis in the infertile patient population is higher (48%) compared with women who undergo tubal sterilisation (5%) (Strathy et al. 1982). Randomised controlled trials have demonstrated that the clinical pregnancy rate after ovarian stimulation or ovarian stimulation IUI was significantly lower in women with minimal and mild endometriosis, than in women with unexplained infertility (Nuoja-Huttunen et al. 1999; Omland et al. 1998). However, controlled trials revealed that the clinical pregnancy rate after ovar-
J Obstet Gynaecol Downloaded from informahealthcare.com by V U L Periodicals Rec on 10/04/14 For personal use only.
Laparoscopy in infertility ian stimulation IUI was higher in women who had received an ablation of endometriotic lesions before ovarian stimulation IUI (Deaton et al. 1990; Tummon et al. 1997). In a multi-centre trial in Canada, women who had minimal and mild endometriosis on diagnostic laparoscopy were randomised to undergo either excision–ablation of endometriotic lesions or expectant management. Laparoscopic surgery increased the cumulative probability of a pregnancy that lasted more than 20 weeks in the first 36 weeks after the procedure (cumulative incidence ratio, 1.7; 95% CI, 1.2–2.6) (Marcoux et al. 1997). In a smaller study in Italy, women with endometriosis-associated infertility were similarly randomised into a laparoscopic surgery group (excision or ablation of endometriotic lesions) or an expectant management group and were followed up for 1 year after laparoscopy. The 1-year birth rates were 19.6% in the resection–ablation group and 22.2% in the expectant management group (Parazzini 1999). In contrast with larger trials in Canada, the results of this study did not support the hypothesis that ablation of endometriotic lesions markedly improves fertility rates. A recent Cochrane meta-analysis, which included studies in Canada and Italy, demonstrated the superiority of laparoscopic surgery over diagnostic laparoscopy according to the on-going pregnancy rate at 20 weeks, the live birth rate with an OR of 1.64 (95% CI, 1.05–2.57) and the clinical pregnancy rates with an OR of 1.66 (95% CI, 1.09–2.51), which favoured laparoscopic surgery (Jacobson et al. 2010). In a retrospective cohort study, Opøien et al. (2011) evaluated the effects of laparoscopic surgery (using ablation of endometriotic lesions) on subsequent IVF/ICSI treatment. Compared with women who only received diagnostic laparoscopy, women who underwent the complete removal of endometriotic lesions had a significantly improved implantation rate (30.9% vs 23.9%, p 0.02), pregnancy rate (40.1% vs 29.4%, p 0.004) and livebirth rate per oocyte retrieval (27.7% vs 20.6%, p 0.04). The surgical removal of minimal and mild endometriotic lesions reduced the time to first pregnancy and resulted in a higher cumulative pregnancy rate. In contrast with minimal and mild endometriosis, distorted anatomy and chronic inflammatory conditions are more predominant in severe endometriosis. The intent of surgery in infertile patients who are affected by moderate to severe endometriosis is to restore normal anatomy through the extirpation of the disease and careful adhesiolysis (Busacca and Olive 2010). This type of surgery will most likely increase the chance of spontaneous conception (Somigliana et al. 2006a,b). In addition, the complete and thorough microsurgical eradication of endometriosis may result in increased spontaneous pregnancies and IVF pregnancies, even after multiple failed IVF cycles (Littman et al. 2005). No prospective studies have compared expectant management and fertility treatment in ART or surgery; however, several case studies have been reported. In these studies, the cumulative pregnancy rate after 1–3 years of surgical treatment was 50% for women with endometriomas and approximately 30% for women with complete cul-de-sac obliteration (Adamson and Pasta 1994; Donnez et al. 1996). One of the most debatable issues regarding the management of endometriosis with IVF, is the presence of an endometrioma. Endometriomas lower pregnancy success rates; however, surgery similarly adversely affects IVF results (Busacca and Olive 2010). An appropriate study design to evaluate the effect of endometriomas on oocyte numbers includes monitoring the response of the ovary with the endometrioma to ovarian stimulation during IVF/ICSI cycles and using the contralateral normal ovary of the same patient as a control. Somigliana et al. (2006a) conducted this type of study in 59 ICSI cycles in 36 patients who had unilateral
3
ovarian endometriomas and who did not undergo previous ovarian surgery. The numbers of co-dominant follicles in intact and affected ovaries (ovaries with an endometrioma) were 4.0 2.2 and 3.0 1.7, respectively (p 0.01). This difference was correlated with a mean reduction of 25% (6–44%) (Somigliana et al. 2006b). This deleterious effect was more evident in women with larger cysts, more than one cyst, and greater responsiveness to ovarian hyperstimulation. Kumbak et al. (2008) investigated whether the space-occupying effect of a 10–50 mm endometrioma, rather than endometriosis, in 85 normal responder patients affected IVF results; 83 normal responder women with 10–35 mm simple ovarian cysts were used as the control group. Fewer oocytes were retrieved in patients with an endometrioma. The grade I embryo ratio and implantation rate were better in the simple ovarian cyst group. The presence of an endometriotic cyst during the IVF cycle was associated with lower embryo quality and a lower implantation rate; however, the pregnancy success rate was unaffected. This adverse effect may be due to the disease and not the presence of a cystic mass. Whether endometrioma excision has a positive or negative effect on IVF success rates has been debated. Garcia Velasco et al. (2004) did not observe a significant difference between the pregnancy rates of 133 women who underwent surgery for endometriomas before IVF (25.4%) and those of 56 subjects who underwent IVF without prior endometrioma removal (22.7%). However, the study was controversial because the diagnosis of an endometrioma in the control group was based on ultrasonography, and they were unable to remove all of the endometriomas due to surgical difficulties. The first RCT to investigate whether endometrioma removal affected subsequent IVF-ICSI cycles was conducted by Demirol et al. (2006). The authors prospectively randomised 99 patients into the following groups: group I (49 patients) underwent conservative ovarian surgery before an ICSI cycle and group II (50 patients) only underwent an ICSI cycle. No significant differences were observed between groups I and II in the fertilisation rate (86% vs 82%), the implantation rate (16.5% vs 18.5%) and the pregnancy rate (34% vs 38%). Because favourable IVF results cannot be obtained from the excision of endometriomas and the risk of decreased ovarian reserves is high with this procedure, a pertinent question is whether we should operate on endometriomas to improve fertility treatment results. The failure to detect an occult early stage malignancy is a rare but important concern (Ness 2003; Van Gorp et al. 2004). The two largest available studies regarding the risk of occult malignancy in endometriotic samples reported frequencies of 0.8% and 0.9% (Mostoufizadeh and Scully 1980; Stern et al. 2001). During ovarian stimulation and/or oocyte collection, endometriomas may rupture and, consequently, cause pelvic infection. The contamination of follicles with endometrioma material due to puncture or rupture is another risk factor of endometriomas. In patients with minimal and mild endometriosis, laparoscopic resection–ablation of endometriosis focal points or adhesions may enhance fecundity in the follow-up period and may improve the outcome of subsequent IVF/ICSI treatment in infertile women (Jacobson et al. 2010; Opøien et al. 2011). If an ovarian endometrioma 4 cm in diameter is present, laparoscopic ovarian cystectomy is recommended to histologically confirm the diagnosis, reduce the risk of infection, improve access to follicles and possibly improve ovarian responses (Kennedy et al. 2005). For infertile women with stage III/IV endometriosis who had previously undergone one or more operations, IVF-ET is a better therapeutic option than another operation for infertility
4
H. Hassa & Y. Aydin
(Practice Committee of the American Society for Reproductive Medicine 2006).
J Obstet Gynaecol Downloaded from informahealthcare.com by V U L Periodicals Rec on 10/04/14 For personal use only.
Laparoscopy after failed ART treatment To the best of our knowledge, no RCTs have evaluated the effect of diagnostic laparoscopy after failed ovulation induction, failed ovarian stimulation IUI or failed ART cycles. In a retrospective study by Ochoa Capelo et al. (2003), diagnostic laparoscopy was performed on 92 patients after four failed cycles of ovulation induction treatment with clomiphene citrate (CC). The laparoscopic findings were normal in only 36% of the cases, whereas endometriosis and/or pelvic adhesions were observed in 50% and 33% of the cases, respectively. Ochoa Capelo et al. (2003) concluded that laparoscopy is a useful tool in the work-up of an infertile couple but did not lead to a significant increase in pregnancy rates following laparoscopic surgery. An important finding regarding the role of laparoscopic evaluation and management after failed IVF cycles was obtained in a retrospective study by Littman et al. (2005). A total of 29 patients who had a mean of 2.2 failed IVF cycles underwent laparoscopic evaluation. The patients who elected not to undergo a laparoscopic procedure were assigned to the control group (35 patients). After the laparoscopic evaluation, 22 cases (76%) conceived, of which 13 conceived spontaneously. Of the patients who were diagnosed with stage I disease, 100% conceived. Overall, 83% of the patients with stage II disease conceived, 83% of the patients with stage III disease conceived and 62% of those with stage IV disease conceived. With the advancement of ART, clinicians are preferentially selecting a new controlled ovarian hyperstimulation/IVF-ICSI cycle after failed ART treatment. It is likely that at least 50% of patient pathologies, such as endometriosis or adhesions, can be detected if laparoscopy is performed after failed IVF treatment; however, no RCTs have confirmed this rate.
Periadnexal adhesions and surgery Pelvic adhesions that result from pelvic infections, endometriosis and previous surgeries may have a role in subfertility (Pabuccu and Gomel 2010). Pelvic adhesions can contribute to tubal dysfunction even if HSG is normal. Periadnexal adhesions may be the sole causative factor for infertility, which encapsulate the fimbriae portion of the patent tube and prevent the oocyte from being captured by otherwise normal fimbria. In addition, periovarian adhesions may adversely affect follicular development (Gomel and McComb 2010). In a controlled case study with a 24-month follow-up, Tulandi and co-workers (1990) demonstrated that adhesiolysis increased pregnancy rates. They compared 69 women who had periadnexal adhesions that were discovered during laparoscopic examination, which were consequently treated with salpingo-ovariolysis by laparotomy, with 78 women who had the same extent of adhesions and who were not treated. They found that the cumulative pregnancy rates at the 12- and 24-month follow-up were 32% and 45% in the treated group and 11% and 16% in the untreated group, respectively. They concluded that treatment with salpingo-ovariolysis is associated with a higher pregnancy rate. Gomel (1983) reported the effect of laparoscopic salpingo-ovariolysis in 92 patients. The duration of infertility was longer than 20 months for all of the patients. In 79 cases, the periadnexal adhesions were severe, and all of these patients were followed-up for at least 9 months. Of the total 92 patients, 57 (62%) achieved at least one intrauterine pregnancy, 54 (58.7%) had one or more full-term pregnancies and five (5.4%) had ectopic pregnancies. Gomel concluded that in a selected patient population and when performed by well-trained operators, laparoscopic salpingo-ovariolysis is a
low-risk procedure that is associated with good spontaneous conception rates and intrauterine pregnancies. In a subsequent RCT by Gurgan et al. (1992), 40 clomiphene citrate-resistant PCOS patients underwent laparoscopic laser photocoagulation of the ovaries and were randomly assigned to either undergo second-look laparoscopy with lysis of adhesions within 3–4 weeks of the initial laparoscopy (n 19) or expectant management (n 20). The pregnancy rates over 6 months were similar in the two groups. The authors concluded that the spontaneous conception rates did not increase during the short time period of 6 months following laparoscopic adhesiolysis. In a 2010 Cochrane review, Duffy et al. (2009) reported on the effect of second-look laparoscopy and adhesiolysis following pelvic reproductive surgery. They found that the odds of pregnancy (OR 0.96, 95% CI, 0.44–2.07) or live birth (OR 0.67, 95% CI, 0.19–2.32) were not significantly different between second-look laparoscopy plus adhesiolysis and no second-look laparoscopy. Pelvic adhesions around the ovaries may interrupt the blood supply to the ovaries, thereby resulting in impaired gonadotropin access to target organs (Nagata et al. 1998). In addition, adhesions may lead to impaired access to the ovary during oocyte pick-up, which results in a decreased number of collected oocytes (Daniell et al. 1983). In contrast, an important treatment for adhesions is a surgical technique known as adhesiolysis. Salpingo-ovariolysis should be performed using the microsurgery principles defined by Gomel (2003, 2010). Facets of microsurgery include: using magnification; employing a technique to minimise tissue injury; preventing foreign body contamination; obtaining meticulous pinpoint haemostasis; identifying proper cleavage planes; completely excising abnormal tissues; precisely aligning and approximating tissue planes and performing a thorough pelvic lavage at the end of the procedure. Using ideal surgical techniques, we can obtain acceptable spontaneous conception rates following salpingo-ovariolysis. However, there is insufficient evidence to recommend performing second-look laparoscopies with adhesiolysis. New RCTs are needed to determine whether performing routine adhesiolysis can improve reproductive outcomes in infertile couples.
Hydrosalpinges Hydrosalpinges adversely affect reproductive outcomes and several factors have been implicated, including a mechanical interference with implantation and toxic effects on the endometrium and embryo (Beyler et al. 1997; Meyer et al. 1997). In 2010, a Cochrane review that included five RCTs with 646 patients examined the effects of interventions on hydrosalpinges before IVF (Johnson et al. 2010). The odds ratio for a clinical pregnancy after undergoing a salpingectomy compared with no surgical treatment was 2.40 (95% CI, 1.49–3.86). The odds ratio for a clinical pregnancy after undergoing a tubal occlusion compared with no surgical treatment was 4.66 (95% CI, 2.17–10.01). According to reproductive performance, neither surgical procedure was superior to the other (salpingectomy compared with occlusion). However, the effects of the procedure were predominant in the ultrasound-visible hydrosalpinx, particularly if the procedure was bilateral (Strandell et al. 1999). Other treatment strategies, such as ultrasound-guided aspiration of hydrosalpingeal fluid at the time of oocyte retrieval, have been suggested as alternative treatments (Van Voorhis et al. 1998) but their effectiveness has not been established and evidence suggests that the fluid reaccumulates rapidly (Bloechle et al. 1997). The negative effects of hydrosalpinges on spontaneous conceptions and IVF pregnancies are well established (Beyler et al. 1997; Meyer et al. 1997). However, with the substantial progress
Laparoscopy in infertility
J Obstet Gynaecol Downloaded from informahealthcare.com by V U L Periodicals Rec on 10/04/14 For personal use only.
in ART, there has been a significant decline in the practice of reconstructive tubal surgery in the form of salpingostomy with a hydrosalpinx indication. Salpingostomy, or salpingoneostomy, is the creation of a new stoma in the fallopian tube with the hydrosalpinx (Gomel 2010). Periadnexal adhesions generally accompany the hydrosalpinx; therefore, the most important predictors of treatment success subsequent to salpingostomy are the degree of pre-existing tubal damage and the extent of periadnexal adhesion. Therefore, salpingo-ovariolysis needs to be completed before a salpingostomy can be performed. Factors that affect the outcome of a salpingostomy include the distal tubal ampulla diameter, the tubal wall thickness, the nature of the tubal endothelium and the extent and type of periadnexal adhesions (Gomel 2003). Reported live birth rates following microsurgical salpingostomy range from 17% to 37% (Gomel 2010). Therefore, in selected cases with tubal factor infertility, laparoscopic salpingostomy may be indicated, which offers the advantage of natural conception.
Laparoscopic ovarian diathermy in PCOS patients The initial steps to improve ovulation in ovulatory PCOS patients include lifestyle modifications, such as weight reduction in overweight patients with dietary restriction and exercise. The next conventional approach is ovulation induction with CC (Gomel and Yarali 2004). Approximately 20% of infertile patients with PCOS will not ovulate on CC. After ovulation failure has been demonstrated with this treatment, clinicians must select the best treatment option for ovulation induction. Ovulation induction with gonadotropins results in high multiple pregnancy rates, up to 25%, and an increased risk of OHSS (Guzick et al. 1999). Another option for treating women with CC resistance (ovulation failure with CC) is laparoscopic ovarian diathermy (LOD), which is an alternative ovarian wedge resection method. However, this method is more invasive and damaging. The common procedure for LOD includes making four punctures per ovary by applying a diathermy current with a specially designed ovarian diathermy needle (Armar et al. 1990; Li et al. 1998). There are various hypotheses regarding the mechanism of action, such as nonspecific stromal destruction or the opening of follicular capsules that release follicular fluid, which contains androgens, thereby removing the ovulation block (Cohen et al. 1972; Gjönnaess 1984). A significant reduction in serum androgen levels, an increase in FSH levels and a decrease in LH pulse amplitude have been observed, independent of the mechanism (Campo 1998). A rapid response following LOD has been reported, such as ovulation within 2–4 weeks and menstruation within 4–6 weeks. In a large RCT, Bayram et al. (2004) reported an ovulation rate of 70% per cycle, a cumulative conception rate of 76% and a live birth rate of 64% following LOD in PCOS patients. Recently, Youssef and Atallah (2007) compared unilateral and bilateral ovarian drilling in 87 patients with PCOS in an RCT and found that the ovulation, pregnancy and miscarriage rates were similar in both groups. Therefore, unilateral drilling is as successful as bilateral drilling but less time-consuming. As clinicians, we must remember that LOD is a surgical procedure. In addition to the general surgical and anaesthetic complications, the most detrimental complications for an infertile couple are pelvic/ovarian adhesions and premature ovarian failure. Mercorio et al. (2008) studied the factors that affect adhesion formation in an RCT. A total of 96 women were randomised into two study groups of 48 women each: one group was treated with six punctures on the left ovary and 12 on the right ovary, and the other group was treated with six punctures on the right ovary and 12 on the left ovary. Using short-term second-look laparoscopy, adhesion formation was detected in 60% of women and in 46% of ovaries.
5
Dense adhesions were more likely to be found on the left ovary, regardless of the number of ovarian punctures performed. Therefore, in LOD cases, we should preferentially select the right ovary for diathermy. Api (2009) investigated whether LOD is harmful to ovarian reserve markers and concluded that there was no evidence of decreased ovarian reserve or premature ovarian failure (POF) associated with LOD in women with PCOS. Most of the changes in the ovarian reserve markers that were observed after LOD could be interpreted as a normalisation of ovarian function rather than a reduction in ovarian reserve. Weerakiet et al. (2007) evaluated ovarian reserve using hormones and ultrasonography in 21 women with PCOS who underwent LOD and compared them with PCOS patients who did not undergo LOD and with normal ovulatory women. The PCOS women who underwent LOD and the PCOS women who did not undergo LOD had a significantly greater ovarian reserve than the age-matched controls. Clinical studies have investigated whether there are any differences between treatment with gonadotropins and LOD. Farquhar et al. (2007) reported that there were no differences in the live birth and clinical pregnancy rates between LOD and gonadotropins and the ORs were 1.04 (95% CI 0.59–1.85) and 1.08 (95% CI 0.69–1.71), respectively. The multiple pregnancy rates were lower with ovarian drilling than with gonadotropins (1% compared with 16%; OR 0.13, 95% CI, 0.03–0.52). There were no differences in the miscarriage rates between the two groups (OR 0.81, 95% CI, 0.36–1.86). In addition, Palomba et al. (2009) concluded that in CC-resistant PCOS patients, LOD should be considered before administering gonadotropins. Within the limits of strict surgical principles, LOD is a better option than ovulation induction with gonadotropins in CCresistant PCOS patients. A major advantage of LOD is a decreased risk of multiple pregnancies. LOD generally results in unifollicular ovulation and does not require intensive follicular monitoring (Thessaloniki ESHRE/ASRM-sponsored PCOS Consensus Workshop Group 2008).
Conclusion Laparoscopy is not a routine part of the diagnostic approach for infertile couples. Every patient and clinical condition must be assessed individually. Regarding tubal occlusion, laparoscopy is recommended when HSG reveals a bilateral obstruction. Laparoscopy can be postponed until at least 10 months after a normal patency or unilateral obstruction is revealed by HSG, particularly in females 36 years of age with normal ovarian reserves. In patients with a history of tuberculosis or severe pelvic infection, laparoscopy should be considered as a first-step approach instead of HSG because in these clinical conditions, tubal morphology and fimbria functional capacity are more important than demonstrating tubal patency. Further randomised controlled trials are warranted to determine whether laparoscopy with IUI should be performed and whether this procedure should be performed before or after IUI. Clinicians should consider the option of diagnostic laparoscopy before IUI in patients with a history of pelvic infection, ectopic pregnancy, tubal surgery or symptoms of endometriosis. In patients with minimal and mild endometriosis, laparoscopic resection–ablation of endometriosis focal points or adhesions may enhance fecundity in the follow-up period and may improve the outcome of subsequent IVF/ICSI treatment in infertile women. If an ovarian endometrioma 4 cm in diameter is present, laparoscopic ovarian cystectomy is recommended to histologically confirm the diagnosis, reduce the risk of infection, improve access
J Obstet Gynaecol Downloaded from informahealthcare.com by V U L Periodicals Rec on 10/04/14 For personal use only.
6
H. Hassa & Y. Aydin
to follicles and possibly improve ovarian response. For infertile women who have stage III/IV endometriosis and who have previously had one or more operations for infertility, IVF-ET is a better therapeutic option than another operation for infertility. No RCTs have evaluated the effects of diagnostic laparoscopy after failed ovulation induction, failed ovarian stimulation IUI or failed ART cycles; however, at least 50% of patient pathologies, such as endometriosis or adhesions, can be detected if laparoscopy is performed. In addition, no evidence suggests that laparoscopy with adhesiolysis before ART increases the pregnancy rate in ART cycles. A hydrosalpinx negatively affects reproductive outcomes. Laparoscopic salpingectomy is indicated in the case of an ultrasound-visible hydrosalpinx. The effect of laparoscopic surgery is more predominant in the presence of a bilateral hydrosalpinx. In selected cases with tubal factor infertility, laparoscopic salpingostomy may be indicated, which offers the advantage of natural conception. LOD is an alternative treatment method to ovulation induction with gonadotropins in patients with CC-resistant PCOS and generally results in unifollicular ovulation. Additionally, LOD allows us to preclude multiple pregnancies and intensive follicular monitoring. Considering the advantages of a low cost, beneficial long-term hormonal effects, a decreased multiple pregnancy risk and the same pregnancy rates as treatment with gonadotropins, we should consider the LOD option in patients with CC-resistant PCOS. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References Adamson GD, Pasta DJ. 1994. Surgical treatment of endometriosis-associated infertility: meta-analysis compared with survival analysis. American Journal of Obstetrics and Gynecology 171:1488–1504. Api M. 2009. Is ovarian reserve diminished after laparoscopic ovarian drilling? Gynecological Endocrinology 25:159–165. Armar NA, McGarrigle HH, Honour J, Holownia P, Jacobs HS, Lachelin GC. 1990. Laparoscopic ovarian diathermy in the management of anovulatory infertility in women with polycystic ovaries: endocrine changes and clinical outcome. Fertility and Sterility 53:45–49. Bayram N, van Wely M, Kaaijk EM, Bossuyt PM, van der Veen F. 2004. Using an electrocautery strategy or recombinant follicle stimulating hormone to induce ovulation in polycystic ovary syndrome: randomised controlled trial. British Medical Journal 328:192. Beyler SA, James KP, Fritz MA, Meyer WR. 1997. Hydrosalpingeal fluid inhibits in-vitro embryonic development in a murine model. Human Reproduction 12:2724–2728. Bloechle M, Schreiner T, Lisse K. 1997. Recurrence of hydrosalpinges after transvaginal aspiration of tubal fluid in an IVF cycle with development of a serometra. Human Reproduction 12:703–705. Bosteels J, Van Herendael B, Weyers S, D’Hooghe T. 2007. The position of diagnostic laparoscopy in current fertility practice. Human Reproduction Update 13:477–485. Busacca M, Olive DL. 2010. Treatment of endometriosis associated infertility. In: Gomel V, Brill AI, editors. Reconstructive and reproductive surgery in gynecology. London: Informa Healthcare. p 84–96. Campo S. 1998. Ovulatory cycles, pregnancy outcome and complications after surgical treatment of polycystic ovary syndrome. Obstetrical and Gynecological Survey 53:297–308. Cohen J, Audebert A, de Brux J, Giorgi H. 1972. Sterility due to dysovulation: prognostic and therapeutic role of ovarian biopsy during calioscopy. Journal de Gynécologie, Obstétrique, et Biologie de la Reproduction 1:657–671. Crosignani PG, Rubin BL; The ESHRE Capri Workshop Group. 2000. Optimal use infertility diagnostic tests and treatments. Human Reproduction 15:723–732. Daniell JF, Pittaway DE, Maxson WS. 1983. The role of laparoscopic adhesiolysis in an in vitro fertilization program. Fertility and Sterility 40:49–52.
Deaton JL, Gibson M, Blackmer KM, Nakajima ST, Badger GJ, Brumsted JR. 1990. A randomised, controlled trial of clomiphene citrate and intrauterine insemination in couples with unexplained infertility or surgically corrected endometriosis. Fertility and Sterility 54:1083–1087. Demirol A, Guven S, Baykal C, Gurgan T. 2006. Effect of endometrioma cystectomy on IVF outcome: a prospective randomized study. Reproductive Biomedicine Online 12:639–643. Donnez J, Nisolle M, Gillet N, Smets M, Bassil S, Casanas-Roux F. 1996. Large ovarian endometriomas. Human Reproduction 11:641–646. Duffy JM, Johnson N, Ahmad G, Watson A. 2009. Postoperative procedures for improving fertility following pelvic reproductive surgery. Cochrane Database of Systematic Reviews (2):CD001897. Evers JL, Land JA, Mol BW. 2003. Evidence-based medicine for diagnostic questions. Seminars in Reproductive Medicine 21:9–15. Farquhar C, Lilford R, Marjoribanks J, Vanderkerchove P. 2007. Laparoscopic drilling by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database of Systematic Reviews (3):CD001122. Garcia-Velasco JA, Mahutte NG, Corona J, Zuniga V, Giles J, Pellicer A. 2004. Removal of endometriomas before in vitro fertilization does not improve fertility outcomes: a matched, case-control study. Fertility and Sterility 81:1194–1206. Gjönnaess H. 1984. Polycystic ovarian syndrome treated by ovarian electrocautery through the laparoscope. Fertility and Sterility 41:20–25. Gomel V, McComb PF. 2010. Investigation of tubal and peritoneal causes of infertility. In: Gomel V, Brill AI, editors. Reconstructive and reproductive surgery in gynecology. 1st ed. London: Informa Healthcare. p 243–259. Gomel V, Taylor PJ. 1995. Diagnostic and operative gynecologic laparoscopy. St Louis: Mosby. p 99–113. Gomel V, Yarali H. 2004. Surgical treatment of polycystic ovary syndrome associated with infertility. Reproductive Biomedicine Online 9:35–42. Gomel V. 1983. Salpingo-ovariolysis by laparoscopy in infertility. Fertility and Sterility 40:607–611. Gomel V. 2003. Reconstructive tubal surgery. In: Rock JA, Jones HW, editors. Te Linde’s operative gynecology. 9th ed. Philadelphia: Lippincott Williams and Wilkins. p 557–595. Gomel V. 2010. Reproductive surgery. In: Gomel V, Brill AI, editors. Reconstructive and reproductive surgery in gynecology. London: Informa Healthcare. p 259–281. Gurgan T, Urman B, Aksu T, Yarali H, Develioglu O, Kisnisci H. 1992. The effect of short interval laparoscopic lysis of adhesions on pregnancy rates following Nd-YAG laser photocoagulation of polycystic ovaries. Obstetrics and Gynecology 80:45–47. Guzick DS, Carson SA, Coutifaris C, Overstreet JW, Factor-Litvak P, Steinkampf MP et al. 1999. Efficacy of superovulation and intrauterine insemination in the treatment of infertility. New England Journal of Medicine 340:177–183. Jacobson TZ, Duffy JM, Barlow D, Farquhar C, Koninekx PR, Olive D. 2010. Laparoscopic surgery for subfertility associated with endometriosis. Cochrane Database of Systematic Reviews (1):CD001398. Johnson N, van Voorst S, Sowter MC, Strandell A, Mol BW. 2010. Surgical treatment for tubal disease in women due to undergo in vitro fertilisation. Cochrane Database of Systematic Reviews (1):CD002125. Kennedy S, Bergqvist A, Chapron C, D’Hooghe T, Dunselman G, Greb R et al.; ESHRE Special Interest Group for Endometriosis Endometrium Guideline Development Group. 2005. ESHRE guideline for the diagnosis and treatment of endometriosis. Human Reproduction 20:2698–2704. Kumbak B, Kahraman S, Karlikaya G, Lacin S, Guney A. 2008. In vitro fertilization in normoresponder patients with endometriomas: comparison with basal simple ovarian cysts. Gynecologic and Obstetric Investigation 65:212–216. Li TC, Saravelos H, Chow MS, Chisabingo R, Cooke ID. 1998. Factors affecting the outcome of laparoscopic ovarian drilling for polycystic ovarian syndrome in women with anovulatory infertility. British Journal of Obstetrics and Gynaecology 105:338–344. Littman E, Giudice L, Lathi R, Berker B, Milki A, Nezhat C. 2005. Role of laparoscopic treatment of endometriosis in patients with failed in vitro fertilization cycles. Fertility and Sterility 84:1574–1508. Maas JW, Evers JL, ter Riet G, Kessels AG. 1997. Pregnancy rate following normal versus abnormal hysterosalpingography findings: a meta-analysis. Gynecologic and Obstetric Investigation 443:79–83. Marcoux S, Maheux R , Berube S. 1997. Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis. New England Journal of Medicine 3337:217–222. Mercorio F, Mercorio A, Di Spiezio Sardo A, Barba GV, Pellicano M, Nappi C. 2008. Evaluation of ovarian adhesion formation after laparoscopic ovarian drilling by second-look minilaparoscopy. Fertility and Sterility 89:1229–1233.
J Obstet Gynaecol Downloaded from informahealthcare.com by V U L Periodicals Rec on 10/04/14 For personal use only.
Laparoscopy in infertility Meyer WR, Castelbaum AJ, Somkuti S, Sagoskin AW, Doyle M, Harris JE et al. 1997. Hydrosalpinges adversely affect markers of endometrial receptivity. Human Reproduction 12:1393–1398. Mol BW, Collins JA, Burrows EA, van der Veen F, Bossuyt PM. 1999. Comparison of hysterosalpingography and laparoscopy in predicting fertility outcome. Human Reproduction 114:1237–1242. Mostoufizadeh M, Scully RE. 1980. Malignant tumors arising in endometriosis. Clinical Obstetrics and Gynecology 23:951–963. Nagata Y, Honjou K, Sonoda M, Makino I, Tamura R, Kawarabayashi T. 1998. Peri-ovarian adhesions interfere with the diffusion of gonadotrophin into the follicular fluid. Human Reproduction 13:2072–2076. Ness RB. 2003. Endometriosis and ovarian cancer: thoughts on shared pathophysiology. American Journal of Obstetrics and Gynecology 189: 280–294. Nuoja-Huttunen S, Tomas C, Bloigu R, Tuomivaara L, Martikainen H. 1999. Intrauterine insemination treatment in subfertility: an analysis of factors affecting outcome. Human Reproduction 14:698–703. Ochoa Capelo F, Kumar A, Steinkampf MP, Azziz R. 2003. Laparoscopic evaluation following failure to achieve pregnancy after ovulation induction with clomiphene citrate. Fertility and Sterility 80:1450–1453. Omland AK, Tanbo T, Dale PO, Abyholm TA. 1998. Artificial insemination by husband in unexplained infertility compared with infertility associated with peritoneal endometriosis. Human Reproduction 13:2602–2605. Opøien HK, Fedorcsak P, Byholm T, Tanbo T. 2011. Complete surgical removal of minimal and mild endometriosis improves outcome of subsequent IVF/ ICSI treatment. Reproductive Biomedicine Online 23:389–395. Pabuccu R, Gomel V. 2010. General principles in preservation of fertility in gynecologic surgery. In: Gomel V, Brill AI, editors. Reconstructive and reproductive surgery in gynecology. 1st ed. London: Informa Healthcare. p 281–285. Palomba S, Falbo A, Zullo F. 2009. Management strategies for ovulation induction in women with polycystic ovary syndrome and known clomifene citrate resistance. Current Opinion in Obstetrics and Gynecology 21:465–473. Parazzini F. 1999. Ablation of lesions or no treatment in minimal-mild endometriosis in infertile women: a randomized trial. Gruppo Italiano per lo Studio dell’Endometriosi. Human Reproduction 14:1332–1334. Practice Committee of the American Society for Reproductive Medicine. 2006. Endometriosis and infertility. Fertility and Sterility 86:156–160. Rowe PJ, Comhaire FH, Hargreave TB, Mahmoud AMA. 1993. WHO manual for the standardized investigation of the infertile couple. Cambridge: Cambridge University Press. Somigliana E, Infantino M, Benedetti F, Arnoldi M, Calanna G, Ragni G. 2006a. The presence of ovarian endometriomas is associated with a reduced responsiveness to gonadotropins. Fertility and Sterility 86:192–196. Somigliana E, Vercellini P, Vigano P, Ragni G, Crosignani PG. 2006b. Should endometriomas be treated before IVF-ICSI cycles? Human Reproduction Update 12:57–64. Speroff L, Fritz MA, editors. 2011. Clinical gynecologic endocrinology and infertility. 8th ed. Philadelphia: Lippincott, Williams and Wilkins. p 1137–1191. Stern RC, Dash R, Bentley RC, Snyder MJ, Haney AF, Robboy SJ. 2001. Malignancy in endometriosis: frequency and comparison of ovarian and
7
extraovarian types. International Journal of Gynecological Pathology 20:133–139. Strandell A, Lindhard A, Waldenstrom U, Thorburn J, Janson PO, Hamberger L. 1999. Hydrosalpinx and IVF outcome: a prospective, randomized multicentre trial in Scandinavia on salpingectomy prior to IVF. Human Reproduction 14:2762–2769. Strathy JH, Molgaard CA, Coulam CB, Melton LJ 3rd. 1982. Endometriosis and infertility: a laparoscopic study of endometriosis among fertile and infertile women. Fertility and Sterility 38:667–672. Swart P, Mol BW, van der Veen F, van Beurden M, Redekop WK, Bossuyt PM. 1995. The accuracy of hysterosalpingography in the diagnosis of tubal pathology: a meta-analysis. Fertility and Sterility 64:486–491. Tanahatoe SJ, Hompes PGA, Lambalk CB. 2003. Accuracy of diagnostic laparoscopy in the infertility work-up before intrauterine insemination. Fertility and Sterility 79:361–366. Tanahatoe SJ, Lambalk CB, Hompes PGA. 2005. The role of laparoscopy in intrauterine insemination: a prospective randomized reallocation study. Human Reproduction 20:3225–3230. Templeton A, Morris JK, Parslow W. 1996. Factors that affect outcome of in-vitro fertilisation treatment. Lancet 348:1402–1406. Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. 2008. Consensus on infertility treatment related to polycystic ovary syndrome. Human Reproduction 23:462–477. Tulandi T, Collins JA, Burrows E, Jarrell JF, McInnes RA, Wrixon W et al. 1990. Treatment-dependent and treatment-independent pregnancy among women with periadnexal adhesions. American Journal of Obstetrics and Gynecology 162:354–357. Tummon IS, Asher LJ, Martin JSB, Tulandi T. 1997. Randomized controlled trial of superovulation and insemination for infertility with minimal or mild endometriosis. Fertility and Sterility 68:8–12. Van Gorp T, Amant F, Neven P, Vergote I and Moerman P. 2004. Endometriosis and the development of malignant tumours of the pelvis. A review of literature. Best Practice and Research. Clinical Obstetrics and Gynaecology 18:349–371. Van Kooij RJ, Looman CW, Habbema JD, Dorland M, te Velde ER. 1996. Age dependent decrease in embryo implantation rate after in vitro fertilization. Fertility and Sterility 66:769–775. Van Voorhis BJ, Sparks AE, Syrop CH, Stovall DW. 1998. Ultrasound guided aspiration of hydrosalpinges is associated with improved pregnancy and implantation rates after in-vitro fertilization cycles. Human Reproduction 13:736–739. Weerakiet S, Lertvikool S, Tingthanatikul Y, Wansumrith S, Leelaphiwat S, Jultanmas R. 2007. Ovarian reserve in women with polycystic ovary syndrome who underwent laparoscopic ovarian drilling. Gynecological Endocrinology 23:455–460. Wordsworth S, Buchanan J, Mollison J, Harrild K, Robertson L, Tay C et al. 2011. Clomifene citrate and intrauterine insemination as first-line treatments for unexplained infertility: are they cost-effective? Human Reproduction 26:369–375. Youssef H, Atallah MM. 2007. Unilateral ovarian drilling in polycystic ovarian syndrome: a prospective randomized study. Reproductive Biomedicine Online 15:457–462.
