Reproductive BioMedicine Online (2014) 28, 137– 140
www.sciencedirect.com www.rbmonline.com
COMMENTARY
Successful twin delivery following transmyometrial embryo transfer in a patient with a false uterine cavity ˜oz a,*, Noemı´ Galindo a, Inmaculada Pe ´rez-Cano a, Marı´a Cruz b, Manuel Mun Juan Antonio Garcı´a-Velasco b a
Instituto Valenciano de Infertilidad, IVI Alicante, Spain;
b
Instituto Valenciano de Infertilidad, IVI Madrid, Spain
* Corresponding author. E-mail address: [email protected] (M Mun ˜oz).
Abstract A successful pregnancy is the greatest goal for reproductive medicine. The probability that pregnancy occurs during a
cycle of assisted reproduction is a function of multiple factors, of which embryo transfer is one of the most critical steps in these treatments. This article reports a case of successful pregnancy and twin delivery by transmyometrial embryo transfer after IVF in a woman with a neocavity parallel to the uterine cavity, which prevented the transfer of embryos to the correct place. The patient first went to another fertility centre where embryo transfer was impossible to perform because the cervix could not be canalized. Subsequently in this study clinic, after considering the difficulty of inserting a catheter into the endometrial cavity, a trial transfer was performed, which discovered a false route parallel to endometrial cavity. Following a first cycle in which conventional transcervical embryo transfer was performed, a transmyometrial embryo transfer was carried out and the patient became pregnant with twins. In cases where transcervical embryo transfer is very difficult or impossible to perform, the value of transmyometrial transfer is self-evident. RBMOnline ª 2013, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. KEYWORDS: false uterine cavity, transmyometrial embryo transfer, Towako, embryo transfer technique, difficult transfer, successful pregnancy
Introduction Embryo transfer is one of the most critical steps among all those involved in assisted fertilization. On the whole, embryo transfer has not received due attention, and the significance of this apparently simple step in success or failure of assisted reproduction is frequently neglected. In an attempt to explain on a quantitative basis the reasons for success or failure of embryo transfer, many investigators have developed models on the relative efficiency of the embryos or uterus in sustaining implantation and three important variables for achieving pregnancy have been identified: transfer efficiency, embryo quality and endometrial receptivity (Pasqualini and Quintans, 2002).
It has been commonly suggested that the ease of transfer is strongly correlated to pregnancy outcome (Munoz et al., 2009; Tomas et al., 2002; Wood et al., 2000). Despite the apparent simplicity of this procedure, difficult transfers often occur and have been shown to significantly lower pregnancy and implantation rates compared with easy transfers. The most common reasons for difficult transfers are cervical stenosis or a large degree of anteroversion/retroversion or anteflexion/retroflexion of the uterus (Garzo, 2006). When transcervical transfer becomes difficult or impossible, an alternative is to perform a transmyometrial transfer with the help of transvaginal ultrasound. This method may be useful in patients with severe cervical stenosis or history
1472-6483/$ - see front matter ª 2013, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.rbmo.2013.09.029
138 of repeated failed IVF cycles in which transfers were extremely difficult. Here is reported a successful twin delivery in a woman with a neocavity parallel to the uterine cavity, which prevented placement of the embryos in the correct hollow.
Case report In 2011, a 44-year-old secondarily infertile woman was referred to this study centre. Tracing back her past history, there had been a normal onset of menarche at 13 years of age with regular cycles; her height was 158 cm and she weighed 53 kg. Her karyotype was normal 46,XX female. She had been diagnosed with mitochondrial myopathy and eyelid ptosis. The male partner was 42 years old; his semen analysis was normal and his medical history revealed no relevant findings. In 2004, the woman underwent a segment transverse Caesarean section following a spontaneous pregnancy; in 2005, a posterior hysterosalpingography by right hydrosalpinx was performed. Three years later (2007) she became pregnant again but she underwent a spontaneous miscarriage at 10 weeks; there was no curettage. The patient presented at the age of 41 years (2008) to another fertility centre with a history of secondary infertility. First, she was prescribed programmed intercourse (3·) but no pregnancy was achieved, and then she was advised to have assisted reproduction treatment, specifically intracytoplasmic sperm injection (ICSI), but the cycle was cancelled due to poor response. Lately, in 2010, she moved to a new fertility centre where she was included in the oocyte donation programme; in this cycle, there was no transfer with fresh embryos because it was impossible to canalize the cervix. Cervical dilatation was performed and finally, she underwent a frozen–thawed embryo transfer; one embryo (day 4) was transferred but the patient did not become pregnant. One year later, in 2011, the patient came to this study centre with a history of failure to conceive for 4 years. Gynaecological and ultrasound examination revealed a retroverted but normal-size uterus and normal ovaries, suggesting that the uterus had healed after the false passage was created. Considering the difficulty to insert a catheter into the endometrial cavity, a trial transfer was performed; in this test, canalization could be done without any difficulty but it was achieved through a false route which ran parallel to the endometrial cavity. Based on these results, we performed a hysteroscopy which reported a cervix leading into a false cavity positioned on the left lateral uterine wall (Figure 1). The internal os was closed due to fibrosis but it was unblocked when the cavity was reached; the uterus was normal with permeable ostiums. In March 2011, as in the previous fertility centre, the patient was included in a oocyte donation programme and she underwent the hormone therapy protocol for oocyte recipients, which consisted in the administration of 0.25 mg/day GnRH antagonist (Cetrotide; Merck-Serono, Madrid, Spain) for the first 7 days of the cycle. Hormone therapy was also initiated on days 1–3 of the cycle and doses of oestradiol valerate (Progynova; Schering-Plough) were increased as follows: 2 mg/day for the first 8 days of treatment, 4 mg/day for the following 3 days, and at least
M Mun ˜oz et al. 6 mg/day until the pregnancy test. On day 15, an ultrasound was performed to evaluate endometrial growth and on the day after donation, 800 mg/day of micronized intravaginal progesterone (Progeffik; Effik Laboratories, Madrid, Spain) was added to the regimen. In this first cycle, nine oocytes were thawed and seven were fertilized via ICSI; at day 5 of development, two blastocyts were selected for transfer but it was not performed because of the complete failure to catheterize the cervix via the transcervical route; the catheter tended to deflect into the false cavity parallel to the true endometrial one; thus blastocysts were cryopreserved until a later attempt. Embryo vitrification was performed according the Cryotop method described by Kuwayama (2007) with slight modifications (Cobo et al., 2010); immediately after warming, embryo survival was determined according to the appearance of blastomeres and the zona pellucida. Blastocyst survival after warming was evaluated according to morphological appearance and the ability of the blastocoele to re-expand before transfer. Two months later, the two cryopreserved blastocysts were warmed and one of them survived. Endometrial preparation was the same as the previous attempt. Considering her cervical and uterine condition, the couple were counselled to have a transmyometrial embryo transfer, thus warmed embryo transfer was performed by the Towako procedure (Figure 2) using a ‘‘Towako’’ catheter (TMET-18G325-325; Kitazato, Japan). The patient was pre-medicated with 2 mg midazolam (Dormicum; Roche Farma, Madrid, Spain) and 50 lm fentanyl (Fentanest; Kern Pharma, Barcelona, Spain). The result of this attempt was a biochemical pregnancy. In October 2011, the couple underwent another attempt. The protocol for hormone therapy was the same as the two previous cycles. In this cycle, 12 oocytes were warmed and nine were fertilized; the patient was pre-medicated as previously and two blastocysts were transferred, under sedation, transmyometrially on day 5 of development. After 14 days, serum b-human chorionic gonadotrophin concentration was 70 mUI/ml, and 2 weeks later, transvaginal ultrasound examination revealed two intrauterine sacs with embryos showing heart activity. Pregnancy continued normally and the patient gave birth, by elective Caesarean section at 38 + 4 weeks of gestation, to a healthy boy (2400 g) and a healthy girl (3000 g). The mother made a good recovery and the post-natal period was uneventful for both the mother and babies.
Discussion There remains a compelling need in the practice of assisted reproduction to evaluate any variables that may influence the implantation rates following IVF/ICSI–embryo transfer. Since the first pregnancy using IVF was achieved nearly 30 years ago, many features of this procedure have undergone significant progress; in contrast, the embryo transfer technique has remained relatively unchanged. Despite it being a critical element in the final step of IVF, embryo transfer has received little attention until recently. Because poor implantation rates have increasingly hindered the growing success of assisted reproduction treatment, the procedure of embryo transfer is now under greater scrutiny.
Successful pregnancy with transmyometrial embryo transfer
Figure 1 point.
139
Images obtained by hysteroscopy. (A) False uterine cavity. (B) Endometrial cavity. (C) Bisection point. (D) Bisection
Towako needle
Endometrium triple layer
Uterus
Figure 2
Ultrasound documentation: insertion of the Towako needle through the endometrium.
Although poor embryo quality or suboptimal uterine receptivity may be responsible for implantation failures, the transfer technique itself is now also recognized as an important determinant of IVF success (Mains and Van Voorhis, 2010). In the current case, all embryo transfers were performed under ultrasound guidance, since it has been shown that this modality does appear to improve the chances of live/ongoing and clinical pregnancies (Brown et al., 2010). Embryo transfer is routinely carried out using the transcervical route; however, this technique is associated with multiple potential negative factors that can result in total
failure of the whole procedure. One of these factors is that the proper placement of the embryos into the uterine cavity may not be achieved because of the failure to pass the catheter through the internal os due to acute utero-cervical angulation, cervical stenosis or anatomical distortion of the cervical canal; therefore, extra care and time should be given to embryo transfer. Before starting ovarian stimulation, it is important to perform an accurate evaluation of the uterine cavity in order to ensure proper placement of the embryos. This trial transfer is important to evaluate the length and direction of
140 the uterine cavity and cervical canal and to choose the most suitable catheter for the embryo transfer; it also helps to discover any unanticipated difficulty in entering the uterine cavity, such as pin-point external os, the presence of cervical polyps or fibroids and/or an anatomical distortion of the cervix from previous surgery or due to congenital anomalies (Mansour and Aboulghar, 2002). In the current case, the trial transfer led to the suspicion of the presence of an intramyometryal neocavity due to the difficulty in reaching the endometrial cavity; this circumstance was later confirmed through hysteroscopy which demonstrated the presence of another cavity that made it difficult to canalize the cervix and to transfer the embryos to the true endometrial cavity. In view of this condition, a transmyometrial embryo transfer was performed as an alternative way to manage this procedure following the Towako method (Kato et al., 1993). Essentially, this technique is relatively simple. The patient is placed in the lithotomy position and the transducer is prepared exactly as for ultrasound-guided oocyte collection. Once the embryos are loaded into the catheter, the needle, fitted with the stylet, is then inserted intravaginally under ultrasound guidance aiming for the middle of the uterine cavity. When the needle is in place, the stylet is removed and the loaded catheter is inserted until its hub is pushed firmly against the luer lock fitting of the needle. The transfer is evident on the ultrasound monitor (Kato et al., 1993). An 18-gauge needle is provided with a trocar to prevent inflow of foreign material during puncture. Although the puncture needle may be inserted under general anaesthesia, experience indicates that local parauterine anaesthesia with 5% lidocaine and epinephrine is enough. The potential complications of such a method are bleeding, injury to adjacent structures, infection and pain; however, the frequency of these complications is very low (Groutz et al., 1997; Kato et al., 1993; Sharif et al., 1996) and a reasonable clinical pregnancy rate has been obtained compared with those derived from conventional transcervical embryo transfer (Groutz et al., 1997; Kato et al., 1993). The technique of embryo transfer is crucial and great attention and time should be given to this step. The pregnancy rate after embryo transfer is dependent on multiple factors including embryo quality, endometrial receptivity and the technique of the embryo transfer itself. Embryo transfer technique has been given little attention and the published data on the subject are minimal and the reason for that is due to the apparent simplicity of the procedure. To most clinicians, it is not a difficult task to insert the embryo transfer catheter and eject the embryos, but unfortunately it is not as simple as it looks and is easier said than done (Wood et al., 2000) Different approaches have been described in cases of difficult embryo transfers with varying success rates. A commonly used initial approach is to negotiate the cervix using the outer sheath of the catheter, with its inner needle withdrawn; alternatively, the cervical route may be bypassed and the embryos may be transferred transmyometrially into the uterine cavity using the Towako method. The importance of the technique by which the embryos are transferred
M Mun ˜oz et al. is reflected in the difference in the pregnancy rates. Although it would only apply to a few cases, transmyometrial transfer could be considered as a possibility for performing embryo transfer in cases where transcervical embryo transfer is very difficult to perform. It is well known that this option is not new, but it is good to remember that this approach exists and is useful in terms of achieving pregnancies in women with problems related to a conventional embryo transfer procedure. Although it is a disused technique due to improvements both in the catheters and the embryo transfer conditions through the use of hysteroscopy, it is still useful in certain cases.
References Brown, J., Buckingham, K., Abou-Setta, A.M., Buckett, W., 2010. Ultrasound versus ‘‘clinical touch’’ for catheter guidance during embryo transfer in women. Cochrane Database Syst. Rev. (Online) 1, CD006107. Cobo, A., Romero, J.L., Perez, S., de los Santos, M.J., Meseguer, M., Remohi, J., 2010. Storage of human oocytes in the vapor phase of nitrogen. Fertil. Steril. 94, 1903–1907. Garzo, V.G., 2006. Embryo transfer technique. Clin. Obstet. Gynecol. 49, 117–122. Groutz, A., Lessing, J.B., Wolf, Y., Azem, F., Yovel, I., Amit, A., 1997. Comparison of transmyometrial and transcervical embryo transfer in patients with previously failed in vitro fertilization-embryo transfer cycles and/or cervical stenosis. Fertil. Steril. 67, 1073–1076. Kato, O., Takatsuka, R., Asch, R.H., 1993. Transvaginal–transmyometrial embryo transfer: the Towako method; experiences of 104 cases. Fertil. Steril. 59, 51–53. Kuwayama, M., 2007. Highly efficient vitrification for cryopreservation of human oocytes and embryos: the cryotop method. Theriogenology 67, 73–80. Mains, L., Van Voorhis, B.J., 2010. Optimizing the technique of embryo transfer. Fertil. Steril. 94, 785–790. Mansour, R.T., Aboulghar, M.A., 2002. Optimizing the embryo transfer technique. Hum. Reprod. 17, 1149–1153. Munoz, M., Meseguer, M., Lizan, C., Ayllon, Y., Perez-Cano, I., Garrido, N., 2009. Bleeding during transfer is the only parameter of patient anatomy and embryo quality that affects reproductive outcome: a prospective study. Fertil. Steril. 92, 953–955. Pasqualini, R.S., Quintans, C.J., 2002. Clinical practice of embryo transfer. Reprod. Biomed. Online 4, 83–92. Sharif, K., Afnan, M., Lenton, W., Bilalis, D., Hunjan, M., Khalaf, Y., 1996. Transmyometrial embryo transfer after difficult immediate mock transcervical transfer. Fertil. Steril. 65, 1071–1074. Tomas, C., Tikkinen, K., Tuomivaara, L., Tapanainen, J.S., Martikainen, H., 2002. The degree of difficulty of embryo transfer is an independent factor for predicting pregnancy. Hum. Reprod. 17, 2632–2635. Wood, E.G., Batzer, F.R., Go, K.J., Gutmann, J.N., Corson, S.L., 2000. Ultrasound-guided soft catheter embryo transfers will improve pregnancy rates in in-vitro fertilization. Hum. Reprod. 15, 107–112. Declaration: The authors report no financial or commercial conflicts of interest. Received 4 February 2013; refereed 17 September 2013; accepted 18 September 2013.
www.sciencedirect.com www.rbmonline.com
COMMENTARY
Successful twin delivery following transmyometrial embryo transfer in a patient with a false uterine cavity ˜oz a,*, Noemı´ Galindo a, Inmaculada Pe ´rez-Cano a, Marı´a Cruz b, Manuel Mun Juan Antonio Garcı´a-Velasco b a
Instituto Valenciano de Infertilidad, IVI Alicante, Spain;
b
Instituto Valenciano de Infertilidad, IVI Madrid, Spain
* Corresponding author. E-mail address: [email protected] (M Mun ˜oz).
Abstract A successful pregnancy is the greatest goal for reproductive medicine. The probability that pregnancy occurs during a
cycle of assisted reproduction is a function of multiple factors, of which embryo transfer is one of the most critical steps in these treatments. This article reports a case of successful pregnancy and twin delivery by transmyometrial embryo transfer after IVF in a woman with a neocavity parallel to the uterine cavity, which prevented the transfer of embryos to the correct place. The patient first went to another fertility centre where embryo transfer was impossible to perform because the cervix could not be canalized. Subsequently in this study clinic, after considering the difficulty of inserting a catheter into the endometrial cavity, a trial transfer was performed, which discovered a false route parallel to endometrial cavity. Following a first cycle in which conventional transcervical embryo transfer was performed, a transmyometrial embryo transfer was carried out and the patient became pregnant with twins. In cases where transcervical embryo transfer is very difficult or impossible to perform, the value of transmyometrial transfer is self-evident. RBMOnline ª 2013, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. KEYWORDS: false uterine cavity, transmyometrial embryo transfer, Towako, embryo transfer technique, difficult transfer, successful pregnancy
Introduction Embryo transfer is one of the most critical steps among all those involved in assisted fertilization. On the whole, embryo transfer has not received due attention, and the significance of this apparently simple step in success or failure of assisted reproduction is frequently neglected. In an attempt to explain on a quantitative basis the reasons for success or failure of embryo transfer, many investigators have developed models on the relative efficiency of the embryos or uterus in sustaining implantation and three important variables for achieving pregnancy have been identified: transfer efficiency, embryo quality and endometrial receptivity (Pasqualini and Quintans, 2002).
It has been commonly suggested that the ease of transfer is strongly correlated to pregnancy outcome (Munoz et al., 2009; Tomas et al., 2002; Wood et al., 2000). Despite the apparent simplicity of this procedure, difficult transfers often occur and have been shown to significantly lower pregnancy and implantation rates compared with easy transfers. The most common reasons for difficult transfers are cervical stenosis or a large degree of anteroversion/retroversion or anteflexion/retroflexion of the uterus (Garzo, 2006). When transcervical transfer becomes difficult or impossible, an alternative is to perform a transmyometrial transfer with the help of transvaginal ultrasound. This method may be useful in patients with severe cervical stenosis or history
1472-6483/$ - see front matter ª 2013, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.rbmo.2013.09.029
138 of repeated failed IVF cycles in which transfers were extremely difficult. Here is reported a successful twin delivery in a woman with a neocavity parallel to the uterine cavity, which prevented placement of the embryos in the correct hollow.
Case report In 2011, a 44-year-old secondarily infertile woman was referred to this study centre. Tracing back her past history, there had been a normal onset of menarche at 13 years of age with regular cycles; her height was 158 cm and she weighed 53 kg. Her karyotype was normal 46,XX female. She had been diagnosed with mitochondrial myopathy and eyelid ptosis. The male partner was 42 years old; his semen analysis was normal and his medical history revealed no relevant findings. In 2004, the woman underwent a segment transverse Caesarean section following a spontaneous pregnancy; in 2005, a posterior hysterosalpingography by right hydrosalpinx was performed. Three years later (2007) she became pregnant again but she underwent a spontaneous miscarriage at 10 weeks; there was no curettage. The patient presented at the age of 41 years (2008) to another fertility centre with a history of secondary infertility. First, she was prescribed programmed intercourse (3·) but no pregnancy was achieved, and then she was advised to have assisted reproduction treatment, specifically intracytoplasmic sperm injection (ICSI), but the cycle was cancelled due to poor response. Lately, in 2010, she moved to a new fertility centre where she was included in the oocyte donation programme; in this cycle, there was no transfer with fresh embryos because it was impossible to canalize the cervix. Cervical dilatation was performed and finally, she underwent a frozen–thawed embryo transfer; one embryo (day 4) was transferred but the patient did not become pregnant. One year later, in 2011, the patient came to this study centre with a history of failure to conceive for 4 years. Gynaecological and ultrasound examination revealed a retroverted but normal-size uterus and normal ovaries, suggesting that the uterus had healed after the false passage was created. Considering the difficulty to insert a catheter into the endometrial cavity, a trial transfer was performed; in this test, canalization could be done without any difficulty but it was achieved through a false route which ran parallel to the endometrial cavity. Based on these results, we performed a hysteroscopy which reported a cervix leading into a false cavity positioned on the left lateral uterine wall (Figure 1). The internal os was closed due to fibrosis but it was unblocked when the cavity was reached; the uterus was normal with permeable ostiums. In March 2011, as in the previous fertility centre, the patient was included in a oocyte donation programme and she underwent the hormone therapy protocol for oocyte recipients, which consisted in the administration of 0.25 mg/day GnRH antagonist (Cetrotide; Merck-Serono, Madrid, Spain) for the first 7 days of the cycle. Hormone therapy was also initiated on days 1–3 of the cycle and doses of oestradiol valerate (Progynova; Schering-Plough) were increased as follows: 2 mg/day for the first 8 days of treatment, 4 mg/day for the following 3 days, and at least
M Mun ˜oz et al. 6 mg/day until the pregnancy test. On day 15, an ultrasound was performed to evaluate endometrial growth and on the day after donation, 800 mg/day of micronized intravaginal progesterone (Progeffik; Effik Laboratories, Madrid, Spain) was added to the regimen. In this first cycle, nine oocytes were thawed and seven were fertilized via ICSI; at day 5 of development, two blastocyts were selected for transfer but it was not performed because of the complete failure to catheterize the cervix via the transcervical route; the catheter tended to deflect into the false cavity parallel to the true endometrial one; thus blastocysts were cryopreserved until a later attempt. Embryo vitrification was performed according the Cryotop method described by Kuwayama (2007) with slight modifications (Cobo et al., 2010); immediately after warming, embryo survival was determined according to the appearance of blastomeres and the zona pellucida. Blastocyst survival after warming was evaluated according to morphological appearance and the ability of the blastocoele to re-expand before transfer. Two months later, the two cryopreserved blastocysts were warmed and one of them survived. Endometrial preparation was the same as the previous attempt. Considering her cervical and uterine condition, the couple were counselled to have a transmyometrial embryo transfer, thus warmed embryo transfer was performed by the Towako procedure (Figure 2) using a ‘‘Towako’’ catheter (TMET-18G325-325; Kitazato, Japan). The patient was pre-medicated with 2 mg midazolam (Dormicum; Roche Farma, Madrid, Spain) and 50 lm fentanyl (Fentanest; Kern Pharma, Barcelona, Spain). The result of this attempt was a biochemical pregnancy. In October 2011, the couple underwent another attempt. The protocol for hormone therapy was the same as the two previous cycles. In this cycle, 12 oocytes were warmed and nine were fertilized; the patient was pre-medicated as previously and two blastocysts were transferred, under sedation, transmyometrially on day 5 of development. After 14 days, serum b-human chorionic gonadotrophin concentration was 70 mUI/ml, and 2 weeks later, transvaginal ultrasound examination revealed two intrauterine sacs with embryos showing heart activity. Pregnancy continued normally and the patient gave birth, by elective Caesarean section at 38 + 4 weeks of gestation, to a healthy boy (2400 g) and a healthy girl (3000 g). The mother made a good recovery and the post-natal period was uneventful for both the mother and babies.
Discussion There remains a compelling need in the practice of assisted reproduction to evaluate any variables that may influence the implantation rates following IVF/ICSI–embryo transfer. Since the first pregnancy using IVF was achieved nearly 30 years ago, many features of this procedure have undergone significant progress; in contrast, the embryo transfer technique has remained relatively unchanged. Despite it being a critical element in the final step of IVF, embryo transfer has received little attention until recently. Because poor implantation rates have increasingly hindered the growing success of assisted reproduction treatment, the procedure of embryo transfer is now under greater scrutiny.
Successful pregnancy with transmyometrial embryo transfer
Figure 1 point.
139
Images obtained by hysteroscopy. (A) False uterine cavity. (B) Endometrial cavity. (C) Bisection point. (D) Bisection
Towako needle
Endometrium triple layer
Uterus
Figure 2
Ultrasound documentation: insertion of the Towako needle through the endometrium.
Although poor embryo quality or suboptimal uterine receptivity may be responsible for implantation failures, the transfer technique itself is now also recognized as an important determinant of IVF success (Mains and Van Voorhis, 2010). In the current case, all embryo transfers were performed under ultrasound guidance, since it has been shown that this modality does appear to improve the chances of live/ongoing and clinical pregnancies (Brown et al., 2010). Embryo transfer is routinely carried out using the transcervical route; however, this technique is associated with multiple potential negative factors that can result in total
failure of the whole procedure. One of these factors is that the proper placement of the embryos into the uterine cavity may not be achieved because of the failure to pass the catheter through the internal os due to acute utero-cervical angulation, cervical stenosis or anatomical distortion of the cervical canal; therefore, extra care and time should be given to embryo transfer. Before starting ovarian stimulation, it is important to perform an accurate evaluation of the uterine cavity in order to ensure proper placement of the embryos. This trial transfer is important to evaluate the length and direction of
140 the uterine cavity and cervical canal and to choose the most suitable catheter for the embryo transfer; it also helps to discover any unanticipated difficulty in entering the uterine cavity, such as pin-point external os, the presence of cervical polyps or fibroids and/or an anatomical distortion of the cervix from previous surgery or due to congenital anomalies (Mansour and Aboulghar, 2002). In the current case, the trial transfer led to the suspicion of the presence of an intramyometryal neocavity due to the difficulty in reaching the endometrial cavity; this circumstance was later confirmed through hysteroscopy which demonstrated the presence of another cavity that made it difficult to canalize the cervix and to transfer the embryos to the true endometrial cavity. In view of this condition, a transmyometrial embryo transfer was performed as an alternative way to manage this procedure following the Towako method (Kato et al., 1993). Essentially, this technique is relatively simple. The patient is placed in the lithotomy position and the transducer is prepared exactly as for ultrasound-guided oocyte collection. Once the embryos are loaded into the catheter, the needle, fitted with the stylet, is then inserted intravaginally under ultrasound guidance aiming for the middle of the uterine cavity. When the needle is in place, the stylet is removed and the loaded catheter is inserted until its hub is pushed firmly against the luer lock fitting of the needle. The transfer is evident on the ultrasound monitor (Kato et al., 1993). An 18-gauge needle is provided with a trocar to prevent inflow of foreign material during puncture. Although the puncture needle may be inserted under general anaesthesia, experience indicates that local parauterine anaesthesia with 5% lidocaine and epinephrine is enough. The potential complications of such a method are bleeding, injury to adjacent structures, infection and pain; however, the frequency of these complications is very low (Groutz et al., 1997; Kato et al., 1993; Sharif et al., 1996) and a reasonable clinical pregnancy rate has been obtained compared with those derived from conventional transcervical embryo transfer (Groutz et al., 1997; Kato et al., 1993). The technique of embryo transfer is crucial and great attention and time should be given to this step. The pregnancy rate after embryo transfer is dependent on multiple factors including embryo quality, endometrial receptivity and the technique of the embryo transfer itself. Embryo transfer technique has been given little attention and the published data on the subject are minimal and the reason for that is due to the apparent simplicity of the procedure. To most clinicians, it is not a difficult task to insert the embryo transfer catheter and eject the embryos, but unfortunately it is not as simple as it looks and is easier said than done (Wood et al., 2000) Different approaches have been described in cases of difficult embryo transfers with varying success rates. A commonly used initial approach is to negotiate the cervix using the outer sheath of the catheter, with its inner needle withdrawn; alternatively, the cervical route may be bypassed and the embryos may be transferred transmyometrially into the uterine cavity using the Towako method. The importance of the technique by which the embryos are transferred
M Mun ˜oz et al. is reflected in the difference in the pregnancy rates. Although it would only apply to a few cases, transmyometrial transfer could be considered as a possibility for performing embryo transfer in cases where transcervical embryo transfer is very difficult to perform. It is well known that this option is not new, but it is good to remember that this approach exists and is useful in terms of achieving pregnancies in women with problems related to a conventional embryo transfer procedure. Although it is a disused technique due to improvements both in the catheters and the embryo transfer conditions through the use of hysteroscopy, it is still useful in certain cases.
References Brown, J., Buckingham, K., Abou-Setta, A.M., Buckett, W., 2010. Ultrasound versus ‘‘clinical touch’’ for catheter guidance during embryo transfer in women. Cochrane Database Syst. Rev. (Online) 1, CD006107. Cobo, A., Romero, J.L., Perez, S., de los Santos, M.J., Meseguer, M., Remohi, J., 2010. Storage of human oocytes in the vapor phase of nitrogen. Fertil. Steril. 94, 1903–1907. Garzo, V.G., 2006. Embryo transfer technique. Clin. Obstet. Gynecol. 49, 117–122. Groutz, A., Lessing, J.B., Wolf, Y., Azem, F., Yovel, I., Amit, A., 1997. Comparison of transmyometrial and transcervical embryo transfer in patients with previously failed in vitro fertilization-embryo transfer cycles and/or cervical stenosis. Fertil. Steril. 67, 1073–1076. Kato, O., Takatsuka, R., Asch, R.H., 1993. Transvaginal–transmyometrial embryo transfer: the Towako method; experiences of 104 cases. Fertil. Steril. 59, 51–53. Kuwayama, M., 2007. Highly efficient vitrification for cryopreservation of human oocytes and embryos: the cryotop method. Theriogenology 67, 73–80. Mains, L., Van Voorhis, B.J., 2010. Optimizing the technique of embryo transfer. Fertil. Steril. 94, 785–790. Mansour, R.T., Aboulghar, M.A., 2002. Optimizing the embryo transfer technique. Hum. Reprod. 17, 1149–1153. Munoz, M., Meseguer, M., Lizan, C., Ayllon, Y., Perez-Cano, I., Garrido, N., 2009. Bleeding during transfer is the only parameter of patient anatomy and embryo quality that affects reproductive outcome: a prospective study. Fertil. Steril. 92, 953–955. Pasqualini, R.S., Quintans, C.J., 2002. Clinical practice of embryo transfer. Reprod. Biomed. Online 4, 83–92. Sharif, K., Afnan, M., Lenton, W., Bilalis, D., Hunjan, M., Khalaf, Y., 1996. Transmyometrial embryo transfer after difficult immediate mock transcervical transfer. Fertil. Steril. 65, 1071–1074. Tomas, C., Tikkinen, K., Tuomivaara, L., Tapanainen, J.S., Martikainen, H., 2002. The degree of difficulty of embryo transfer is an independent factor for predicting pregnancy. Hum. Reprod. 17, 2632–2635. Wood, E.G., Batzer, F.R., Go, K.J., Gutmann, J.N., Corson, S.L., 2000. Ultrasound-guided soft catheter embryo transfers will improve pregnancy rates in in-vitro fertilization. Hum. Reprod. 15, 107–112. Declaration: The authors report no financial or commercial conflicts of interest. Received 4 February 2013; refereed 17 September 2013; accepted 18 September 2013.
