1i
.
4
Assisted reprqductive technologyl FERTILITY AND STERILITY Copyright If) 1992 The American Fertility Society
Vol. 58, No.4, October 1992 Printed on acid-free paper in U.S.A.
The effects of spontaneous luteinizing hormone surges on superovulatory cycles
James W. Akin, M.D.* Marguerite K. Shepard, M.D. H. Jana Sandefur, M.S.N. Kim K. Cox, M.S.N. Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana
Objective: To determine the effect of a spontaneous luteinizing hormone (LH) surge on the cycle fecundity during superovulation induction. Design: Superovulatory cycles of patients with various diagnoses are retrospectively compared. Setting: Reproductive Endocrinology Outpatient Clinic. Patients: A total of 1,185 superovulatory cycles from July 1, 1982 until November 1, 1991 are compared. Main Outcome Measure: The probability of achieving a pregnancy per treatment cycle. Results: Patients with unexplained infertility and hyperprolactinemia were more likely to have a spontaneous LH surge during superovulation than patients with either endometriosis or polycystic ovarian disease. However, the cycle fecundity rate did not differ whether or not an LH surge occurred, regardless of the diagnosis. Conclusions: Spontaneous onset of an LH surge during superovulation induction does not inFertil SterilI992;58:740-3 fluence the chances for pregnancy. Key Words: Superovulation, menotropins, infertility, endometriosis, luteinizing hormone
Human menopausal gonadotropin (hMG) therapy has become an integral part of the various stimulation protocols for patients undergoing in vitro fertilization (IVF) and gamete intrafallopian tube transfer (GIFT). Undoubtedly, hMG use increases the number of oocytes that are retrieved and perhaps the overall chances for successful pregnancy. Before the advent of IVF and GIFT, experience with hMG therapy was frequently limited to ovulation induction in anovulatory patients. More recently, patients with other diagnoses have benefited from the empirical use of hMG in stimulation protocols not associated with the retrieval of oocytes. The overall
Received December 23, 1991; revised and accepted June 8, 1992. * Reprint requests: James W. Akin, M.D., Department of Obstetrics and Gynecology, Indiana University Hospital, Room 2440, 926 West Michigan Street, Indianapolis, Indiana 46202. 740
Akin et al.
LH and superovulation
increased use of hMG has prompted closer scrutiny of many of the drug's actions. Numerous studies have evaluated the effects of spontaneous luteinizing hormone (LH) surges on IVF success rates when hMG was used either alone or with clomiphene citrate but in the absence of pituitary suppression. Huang et al. (1) described 75 patients undergoing 109 IVF cycles with an endogenous LH surge rate of 42%. Although a lower fertilization and cleavage rate was seen in the endogenous surge group, the pregnancy rates (PRs) did not differ. A review of 1,533 IVF cycles by Wood et al. (2) revealed an increased PR in cycles in which an endogenous LH surge had occurred. Conversely, Lejeune et al. (3) recommended canceling any cycle in which a spontaneous LH surge was present because the PR was much lower. Finally, Foulot et al. (4) studied patients undergoing IVF in unstimulated cycles. They found an increased PR if no LH surge Fertility and Sterility
had occurred, although no difference was seen in the number of oocytes retrieved. Although it is not difficult to surmise that ovulation before oocyte retrieval will ultimately decrease PRs, the above studies frequently found no difference in the number of oocytes retrieved whether or not an endogenous LH surge had occurred. It is possible that other factors may have transpired to have caused the discrepancy of PRs. Still, conclusions on what effect endogenous LH surges have on IVF PRs remain controversial at best. The significance of a spontaneous LH surge in patients receiving hMG superovulation induction for subsequent timed intercourse or intrauterine insemination (lUI) may be entirely different. We were unable to locate any studies dealing with this particular question. The purpose of the present study is to ascertain whether the spontaneous onset of an LH surge has either positive or negative effects on the cycle fecundity rate in this population in lieu of the conflicting, yet suggestive, data from IVF. MATERIALS AND METHODS
The study population consisted of 1,185 cycles of hMG superovulation evaluated retrospectively in patients with various diagnoses who were treated between July 1, 1982, and November 1, 1991. Diagnostic evaluation of patients included a physical examination, semen analysis, postcoital test (PCT), and laparoscopy. Patients presenting with habitual abortion were also found to have either a normal hysterosalpingogram or hysteroscopy, normal karyotypes, and normal thyroid studies. A laparoscopy was not always performed in cases of habitual abortion before treatment with hMG. Patients with tubal disease had at least one patent fallopian tube. Each patient received hMG injections daily beginning between cycle days 3 and 5 and continuing until a follicle of 18 mm mean diameter was seen on sonogram with appropriate estradiol (E 2) levels, unless an LH surge had spontaneously begun as described below. All patients then received 10,000 IU of human chorionic gonadotropin (hCG) by injection to stimulate ovulation. The patients underwent either timed intercourse or lUI according to the results of the PCT or empirically based on patient preference. Pregnancy was defined by a delay in menses and a rising serum hCG. Serum LH levels were obtained on a daily basis in the early morning hours beginning on the day of the first preovulatory sonogram. If a rise in the LH level had begun, hCG was given, and the patient Vol. 58, No.4, October 1992
underwent either timed intercourse or an lUI regardless of the follicular measurements or the serum E2 level. Assays were run on a daily basis by the Indiana University Hospital Clinical Chemistry Laboratory. Two different assays were used in determining the serum LH levels. From July 1, 1982, until January 1, 1990, a radioimmunoassay (RIA) kit by Amersham (Arlington Heights, IL) was used. The 95% confidence interval (CI) of LH for a follicular phase female was 3.7 to 31.2 lUlL. The interassay and intra-assay coefficients of variation (CV) were each
.
4
Assisted reprqductive technologyl FERTILITY AND STERILITY Copyright If) 1992 The American Fertility Society
Vol. 58, No.4, October 1992 Printed on acid-free paper in U.S.A.
The effects of spontaneous luteinizing hormone surges on superovulatory cycles
James W. Akin, M.D.* Marguerite K. Shepard, M.D. H. Jana Sandefur, M.S.N. Kim K. Cox, M.S.N. Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana
Objective: To determine the effect of a spontaneous luteinizing hormone (LH) surge on the cycle fecundity during superovulation induction. Design: Superovulatory cycles of patients with various diagnoses are retrospectively compared. Setting: Reproductive Endocrinology Outpatient Clinic. Patients: A total of 1,185 superovulatory cycles from July 1, 1982 until November 1, 1991 are compared. Main Outcome Measure: The probability of achieving a pregnancy per treatment cycle. Results: Patients with unexplained infertility and hyperprolactinemia were more likely to have a spontaneous LH surge during superovulation than patients with either endometriosis or polycystic ovarian disease. However, the cycle fecundity rate did not differ whether or not an LH surge occurred, regardless of the diagnosis. Conclusions: Spontaneous onset of an LH surge during superovulation induction does not inFertil SterilI992;58:740-3 fluence the chances for pregnancy. Key Words: Superovulation, menotropins, infertility, endometriosis, luteinizing hormone
Human menopausal gonadotropin (hMG) therapy has become an integral part of the various stimulation protocols for patients undergoing in vitro fertilization (IVF) and gamete intrafallopian tube transfer (GIFT). Undoubtedly, hMG use increases the number of oocytes that are retrieved and perhaps the overall chances for successful pregnancy. Before the advent of IVF and GIFT, experience with hMG therapy was frequently limited to ovulation induction in anovulatory patients. More recently, patients with other diagnoses have benefited from the empirical use of hMG in stimulation protocols not associated with the retrieval of oocytes. The overall
Received December 23, 1991; revised and accepted June 8, 1992. * Reprint requests: James W. Akin, M.D., Department of Obstetrics and Gynecology, Indiana University Hospital, Room 2440, 926 West Michigan Street, Indianapolis, Indiana 46202. 740
Akin et al.
LH and superovulation
increased use of hMG has prompted closer scrutiny of many of the drug's actions. Numerous studies have evaluated the effects of spontaneous luteinizing hormone (LH) surges on IVF success rates when hMG was used either alone or with clomiphene citrate but in the absence of pituitary suppression. Huang et al. (1) described 75 patients undergoing 109 IVF cycles with an endogenous LH surge rate of 42%. Although a lower fertilization and cleavage rate was seen in the endogenous surge group, the pregnancy rates (PRs) did not differ. A review of 1,533 IVF cycles by Wood et al. (2) revealed an increased PR in cycles in which an endogenous LH surge had occurred. Conversely, Lejeune et al. (3) recommended canceling any cycle in which a spontaneous LH surge was present because the PR was much lower. Finally, Foulot et al. (4) studied patients undergoing IVF in unstimulated cycles. They found an increased PR if no LH surge Fertility and Sterility
had occurred, although no difference was seen in the number of oocytes retrieved. Although it is not difficult to surmise that ovulation before oocyte retrieval will ultimately decrease PRs, the above studies frequently found no difference in the number of oocytes retrieved whether or not an endogenous LH surge had occurred. It is possible that other factors may have transpired to have caused the discrepancy of PRs. Still, conclusions on what effect endogenous LH surges have on IVF PRs remain controversial at best. The significance of a spontaneous LH surge in patients receiving hMG superovulation induction for subsequent timed intercourse or intrauterine insemination (lUI) may be entirely different. We were unable to locate any studies dealing with this particular question. The purpose of the present study is to ascertain whether the spontaneous onset of an LH surge has either positive or negative effects on the cycle fecundity rate in this population in lieu of the conflicting, yet suggestive, data from IVF. MATERIALS AND METHODS
The study population consisted of 1,185 cycles of hMG superovulation evaluated retrospectively in patients with various diagnoses who were treated between July 1, 1982, and November 1, 1991. Diagnostic evaluation of patients included a physical examination, semen analysis, postcoital test (PCT), and laparoscopy. Patients presenting with habitual abortion were also found to have either a normal hysterosalpingogram or hysteroscopy, normal karyotypes, and normal thyroid studies. A laparoscopy was not always performed in cases of habitual abortion before treatment with hMG. Patients with tubal disease had at least one patent fallopian tube. Each patient received hMG injections daily beginning between cycle days 3 and 5 and continuing until a follicle of 18 mm mean diameter was seen on sonogram with appropriate estradiol (E 2) levels, unless an LH surge had spontaneously begun as described below. All patients then received 10,000 IU of human chorionic gonadotropin (hCG) by injection to stimulate ovulation. The patients underwent either timed intercourse or lUI according to the results of the PCT or empirically based on patient preference. Pregnancy was defined by a delay in menses and a rising serum hCG. Serum LH levels were obtained on a daily basis in the early morning hours beginning on the day of the first preovulatory sonogram. If a rise in the LH level had begun, hCG was given, and the patient Vol. 58, No.4, October 1992
underwent either timed intercourse or an lUI regardless of the follicular measurements or the serum E2 level. Assays were run on a daily basis by the Indiana University Hospital Clinical Chemistry Laboratory. Two different assays were used in determining the serum LH levels. From July 1, 1982, until January 1, 1990, a radioimmunoassay (RIA) kit by Amersham (Arlington Heights, IL) was used. The 95% confidence interval (CI) of LH for a follicular phase female was 3.7 to 31.2 lUlL. The interassay and intra-assay coefficients of variation (CV) were each
