Adjunctive leuprolide therapy does not improve cycle fecundity in controlled ovarian hyperstimulation and intrauterine insemination of subfertile women

Problems arising from controlled ovarian hyperstimulation for intrauterine insemination, such as premature luteinization and asynchronous ovarian follicular development, are identical to those encountered with controlled ovarian hyperstimulation for in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT). It has been suggested that the adjunctive use of GnRH agonists for controlled ovarian hyperstimulation improves the efficiency of GIFT and IVF cycles. We hypothesized that adjunctive use of leuprolide acetate, a GnRH agonist, would have a similarly beneficial effect on cycle quality and cycle fecundity in subfertile women treated with controlled ovarian hyperstimulation and intrauterine insemination. We randomly assigned the first cycle of controlled ovarian hyperstimulation and intrauterine insemination for each of 97 subfertile women to include either human menopausal gonadotropins (hMGs) alone or hMGs following midluteal pre-treatment with leuprolide. If a pregnancy did not occur in the first cycle, the woman was given the other treatment in the second cycle. Although the cycles that included leuprolide required a larger amount of hMGs and more days of stimulation per cycle, the mean estradiol concentrations and numbers of follicles were not different. Despite prevention of premature luteinization with leuprolide, the cycle fecundity was not different between groups (0.11 with adjunctive leuprolide treatment and 0.22 with hMGs alone). We conclude that in unselected subfertile patients, the adjunctive use of leuprolide for controlled ovarian hyperstimulation and intrauterine insemination does not improve cycle fecundity compared with treatment cycles that do not include adjunctive leuprolide therapy.     

Ultrasonographic and clinical correlates of menotropin versus sequential clomiphene citrate: menotropin therapy for induction of ovulation

Forty-six women remaining infertile with clomiphene citrate (CC) with or without human chorionic gonadotropin (hCG) were treated by either human menopausal gonadotropin (hMG, 44 cycles) or CC + hMG (33 cycles) and monitored by serum estradiol (E2) and ultrasonography. Ovarian hyperstimulation syndrome (OHS) and pregnancy outcome were compared in both regimens. In the presence of dominant follicles (greater than or equal to 18 mm) alone or with a single secondary follicle (14 to 16 mm) at hCG administration, OHS did not develop. A significant increase in OHS was noted when three or more secondary follicles were observed. Overall pregnancy rates were similar in both regimens but significantly higher when hCG was injected before rather than after the E2 peak. The results suggest secondary follicles rather than dominant follicles are a valuable sign of possible OHS development; and CC + hMG should be considered in CC-failure patients.     

Cycle fecundity in controlled ovarian hyperstimulation and intrauterine insemination. Influence of the number of mature follicles at hCG administration

OBJECTIVE: To determine if cycle fecundity in controlled ovarian hyperstimulation (COH) with intrauterine insemination (IUI) cycles is influenced by the number of mature follicles at the time of hCG administration. STUDY DESIGN: Retrospective data analysis of 75 infertility patients undergoing 164 consecutive COH/IUI cycles with FSH and/or hMG in a university-affiliated private infertility center. Cycles were compared for number of mature follicles (> or = 15 mm) and peak serum estradiol levels, total number of ampules and days of gonadotropin use, and clinical pregnancy rate. RESULTS: There was a statistically significant increase in cycle fecundity when three to four mature follicles were stimulated. Peak estradiol levels were significantly different in the groups, as predicted from the number of follicles. The groups were not statistically different in age or etiology of infertility. Group A (1-2 mature follicles) required significantly more FSH/hMG than group B (3-4 follicles) or group C (> or = 5 follicles). CONCLUSION: In COH/IUI cycles, three to four mature follicles yield improved cycle fecundity as compared to that in cycles with a smaller or larger number of follicles. These findings may help identify patients who will be more successful in conceiving with COH/IUI versus those who should be counseled to use other assisted reproductive technologies.     

Clinical characteristics of ovulation induction with human menopausal gonadotropins with and without leuprolide acetate in polycystic ovary syndrome

Ovulation induction in polycystic ovary syndrome (PCOS) with human menopausal gonadotropins (hMG) results in suboptimal cycle fecundity and frequently is complicated by ovarian hyperstimulation. The use of a gonadotropin releasing-hormone agonist (Gn-RH-a) with hMG induction of ovulation may improve the therapeutic outcome. In this prospective, randomized trial, 27 women with PCOS underwent a total of 25 cycles of hMG alone and 33 cycles with adjunctive GnRH-a (leuprolide) treatment. Premature luteinization was seen less frequently in the leuprolide-treated cycles than in cycles treated with hMG alone. There were no differences between the treatments in ovarian sensitivity to hMG. Cycle fecundity was 0.16 for hMG alone cycles, and 0.27 for leuprolide with hMG cycles, which were not statistically different. We conclude that the sensitivity of the PCOS ovary to hMG is not affected by 4 weeks of leuprolide pretreatment.     

The Antral Follicle Count Predicts the Outcome of Pregnancy in a Controlled Ovarian Hyperstimulation/Intrauterine Insemination Program

Purpose: Our purpose was to test whether age-related changes in antral follicle counts can predict the pregnancy outcome in the early follicular phase of a controlled ovarian hyperstimulation/intrauterine insemination (COH/IUI) program. Methods: A selected group of 107 women (36 healthy women requesting child sex preselection, 52 women with unexplained infertility, and 19 with minimal endometriosis) who underwent controlled ovarian hyperstimulation with clomiphene citrate (CC) plus human menopausal gonadotrophin (hMG) and subsequent intrauterine insemination were enrolled in the study. Transvaginal ultrasonography (7.0 MHz) was used to determine the total number of antral follicles (2–8 mm) in the right and left ovaries. The association among the antral follicle count, age, dominant follicle, and estradiol (E ₂ ) level on the day of human chorionic gonadotropin (hCG) was analyzed. The association of the pregnancy rate and OHSS with the antral follicle count, dominant follicle count, and age was also examined. Results: The total antral follicle number decreased with age (P<0.0001). Dominant follicle number increased with total antral follicle number in women who received CCplus hMG/ IUI (P<0.0001). The pregnant group had a higher number of antral follicle and dominant follicles in comparison with the nonpregnant group (P<0.01 and P<0.02, respectively). The E ₂ level on the day of hCG injection increased positively with the total number of antral follicles (P<0.0001) and the total number of dominant follicles (P<0.0001). In women aged younger than 35 years, the pregnancy rate and dominant follicle number rose as the number of antral follicles increased (P<0.03 and P<0.0001, respectively). The pregnancy rate was low (2/39) in women aged older than 35 years regardless of the number of antral follicles (P<0.05) and the extent of hMG administration (P<0.02). Women aged older than 35 also produced fewer dominant follicles (P<0.001). No pregnancy was achieved in a patient with an antral follicle number of less than five (17 cases). Conclusions: Age-related changes in antral follicle count significantly predicted the dominant follicle count and the pregnancy outcome. In women with antral follicle counts of less than five or who are older than 35 years, the application of COH/IUI may not be indicated.     

Superovulation with or without intrauterine insemination for the treatment of infertility.

Patients undergoing human menopausal gonadotropin (hMG) superovulation were reviewed retrospectively to determine whether fecundity was greater for intrauterine insemination (IUI) than timed intercourse. Forty patients with unexplained infertility, American Fertility Society I or II endometriosis, luteal phase defect and/or cervical factor were treated with hMG alone or hMG plus IUI. Twenty-eight underwent 52 cycles of hMG/IUI, and 19 underwent 31 cycles of hMG. The probability of pregnancy after four cycles was significantly better in the hMG/IUI group (.90) than the hMG group (.37, P = .049). There was a 54.5% multiple pregnancy rate, and one patient was admitted to the hospital for hyperstimulation. When traditional therapy fails, hMG/IUI significantly increases the pregnancy rates as compared to hMG with timed intercourse in a "good prognosis" group of patients.     

促性腺激素释放激素激动剂超短方案在超促排卵中的应用

目的：探讨促性腺激素释放激素激动剂（ＧｎＲＨ－ａ）超短方案在促排卵中的作用。方法：以采用克罗米芬联合人绒毛膜促性腺激素（ＣＣ／ｈＣＧ组，５０个周期、３１例），及克罗米芬联合人绝经期促性腺激素、绒毛膜促性腺激素（ＣＣ／ｈＭＧ／ｈＣＧ组，１６个周期、１６例）方案者为对照，对比ＧｎＲＨ－ａ超短方案联合人绝经期促性腺激素、绒毛膜促性腺激素方案者（ＧｎＲＨ－ａ超短方案／ｈＭＧ／ｈＣＧ组，１５个周期、１５例）ｈＣＧ注射日激素水平、优势卵泡个数、子宫内膜厚度、宫颈评分及妊娠率。ＧｎＲＨ－ａ超短方案／ｈＭＧ／ｈＣＧ组全部来自采用ＣＣ助孕失败或采用ＣＣ／ｈＭＧ／ｈＣＧ方案显示卵巢反应性差的患者。结果：ＣＣ／ｈＭＧ／ｈＣＧ组有３例（１８．８％）发生过早黄素化。ＧｎＲＨ－ａ超短方案／ｈＭＧ／ｈＣＧ组ｈＣＧ注射日血清黄体生成素（ＬＨ）水平明显低于对照组，其优势卵泡个数、子宫内膜厚度及宫颈评分都明显高于对照组，差异均具有显著性（Ｐ＜０．０５）。３组周期妊娠率相近。结论：ＧｎＲＨ－ａ超短方案／ｈＭＧ／ｈＣＧ方案为一种较好的促超排卵方案，对ＣＣ助孕失败及ＣＣ／ｈＭＧ／ｈＣＧ方案卵巢反应性差的患者仍有较好的效果。     

Addition of gonadotrophin-releasing hormone agonist and/or two inseminations with husband's sperm do not improve the pregnancy rate in superovulated cycles

BACKGROUND: A prospective randomized study was performed to evaluate the addition of a gonadotropin releasing hormone agonist (GnRH-a) during treatment with human menopausal gonadotropins (hMG) in cycles with artificial inseminations with husband's washed sperm (AIH). We also compared the pregnancy rate per cycle after one versus two AIHs. METHODS: We designed a 22 factorial trial. A total of 172 couples with unexplained infertility (n=88), endometriosis (n=39), or cervical (n=24) or male (n=21) factors were included, of whom 161 fulfilled the inclusion criteria and treatment. Eighty-one women were treated with GnRH-a/hMG and another 80 with hMG only, respectively. RESULTS: The pregnancy rates did not differ between the two stimulation protocols (12% for GnRH-a/hMG and 9% for hMG). With GnRH-a/hMG more follicles >15 mm (3.4 and 2.4, respectively; p<0.01) and a higher multiple pregnancy rate after 20 weeks of gestation were observed (55% vs. 0%; p<0.05). Eighty-seven women were treated with one AIH, whereas 65 women received two AIHs on two consecutive days. The pregnancy rates were similar in these two groups (11% and 9% respectively; n.s.) CONCLUSION: It is concluded that neither addition of GnRH-a before and during controlled ovarian hyperstimulation nor two AIHs compared with one single AIH per cycle has a beneficial effect on the pregnancy rate. However, GnRH-a increases the risk for multiple pregnancies.     

Follicular fluid steroid content and in vitro steroid secretion by granulosa-lutein cells from individual follicles among different stimulation protocols for in vitro fertilization-embryo transfer

The in vitro steroidogenic capacity of granulosa-lutein (G-L) cells aspirated from individual follicles during cycles of in vitro fertilization-embryo transfer was examined and compared among three different stimulation protocols: human menopausal gonadotropins (hMG), clomiphene citrate (CC) and hMG, and follicle stimulating hormone (FSH). In addition, the clinical outcome of the patients in each protocol was examined. After 3 days of culture in basal medium, fresh medium with or without androstenedione (A) (10^–7 M) was added for 24 hr, at which time medium was obtained for measurement of progesterone (P) and estradiol (E) content. Follicular fluid (FF) P, E, and A were measured in each follicle and compared among protocols. FF from individual follicles in patients stimulated with FSH contained higher levels of P compared to FF from patients stimulated with hMG or CC/hMG, while E was higher in patients stimulated with CC/hMG compared to FSH or hMG. FF levels of A were not significantly different among the protocols. In vitro steroid secretion revealed a progressive, increase in P secretion in contrast to decreasing E secretion when one compares CC/hMG, hMG, and FSH. Patients undergoing ovarian hyperstimulation with FSH had significantly more atretic oocytes identified at the time of oocyte harvest compared to patients undergoing ovarian hyperstimulation with CC/hMG or hMG. The hMG protocol yielded significantly fewer fertilized oocytes, cleaved embryos, and transferred embryos, compared to the CC/hMG and FSH protocol, however, there was no significant difference in pregnancy rate among the three protocols. These data demonstrate that individual follicles contain G-L cells with markedly different abilities to luteinize in vitro as assessed by steroid secretion. Furthermore, the in vitro steroidogenic capacity of G-L cells tends to reflect the steroid profile found in the follicular fluid at the time of harvest. The marked variability in in vitro steroid secretion of G-L cells from the same follicle cohort suggests that attempts to induce multiple follicular development may not necessarily lead to synchronous development of all follicles in an individual patient.     

Relationship of follicle numbers and estradiol levels to multiple implantation in 3,608 intrauterine insemination cycles

OBJECTIVE: To determine the relationship of follicle numbers and estradiol (E(2)) levels to multiple implantations in human menopausal gonadotropin (hMG) and clomiphene citrate (CC) cycles. DESIGN: Fifteen-year prospective study. SETTING: Private infertility clinic. PATIENT(S): Women who underwent 3608 cycles of husband or donor intrauterine insemination (IUI). INTERVENTION(S): Ovulation induction (OI) with CC, hMG, or CC+hMG. MAIN OUTCOME MEASURE(S): Pregnancy and multiple implantations. RESULT(S): Triplet and higher-order implantations-but not twin implantations-were related to age, E(2) levels, and number of follicles > or = 12 mm and > or = 15 mm, but not number of follicles > or = 18 mm, in hMG and CC+hMG cycles. For patients less than 35 years old, three or more implantations tripled when six or more follicles were > or = 12 mm, in CC, hMG, and CC+hMG cycles, and when E(2) was > or = 1000 pg mL in hMG and CC+hMG cycles. For patients 35 or older, pregnancy rates in hMG and CC+hMG cycles doubled when six or more follicles were > or = 12 mm, or E(2) levels were >1000 pg mL, whereas 3 or more implantations were not significantly increased. CONCLUSIONS: Withholding hCG or IUI in CC, hMG, and CC+hMG cycles when six or more follicles are > or = 12 mm may reduce triplet and higher-order implantations by 67% without significantly reducing pregnancy rates for patients under 35 years of age.     

Successful Pregnancies in Patients with Estrogenic Anovulation After Low-Dose Human Chorionic Gonadotropin Therapy Alone Following hMG for Controlled Ovarian Hyperstimulation

Objective: To demonstrate that folliculogenesis can be sustained with 200 IU human chorionic gonadotropins (hCG) after FSH-priming and result in pregnancy in women with estrogenic ovulatory dysfunction and risk factors for severe ovarian hyperstimulation syndrome (OHSS).Design: Case report: Three women with infertility associated with estrogenic ovulatory dysfunction and hyperinsulinemia who appeared to be at high risk for severe OHSS during gonadotropin therapy.Interventions: After 10 days of receiving either 150 IU hMG or recombinant FSH, patients were switched to 200 IU hCG/day alone for 2–3 days. 5,000 IU of hCG was then administered followed by either home intercourse, intrauterine insemination or transvaginal oocyte retrieval-embryo transfer.Main Outcome Measures: Endovaginal ultrasound measurement of follicle number and size, serum estradiol levels, symptoms of ovarian hyperstimulation, pregnancy test, and evaluation of pregnancy by transvaginal ultrasound.Results: After discontinuation of hMG or recombinant FSH, serum estradiol concentrations continued to rise, and follicles > 14 mm continued to grow during low-dose hCG administration. All women conceived without developing symptoms of OHSS. Pregnancy outcomes achieved include a term singleton delivery, a term twin delivery, and triplets delivered at 31 weeks gestation.Conclusion: The use of low-dose hCG alone is sufficient for supporting the late stages of folliculogenesis in women with estrogenic ovulatory dysfunction. This ovulation induction regimen appears to support the follicular growth of larger follicles while decreasing the number of smaller preovulatory follicles, thereby reducing a known risk factor for OHSS. We report on the positive pregnancy outcomes in 3 women with estrogenic ovulatory dysfunction and clinically appeared to be at high risk for developing severe OHSS who safely underwent this protocol.     

A prospective, randomized trial comparing two different intrauterine insemination regimens in controlled ovarian hyperstimulation cycles.

OBJECTIVE: To compare a single periovulatory intrauterine insemination (IUI) with a regimen employing two IUIs, one before ovulation and one after ovulation, in patients undergoing controlled ovarian hyperstimulation with human menopausal gonadotropins (hMG) combined with human chorionic gonadotropin (hCG). DESIGN: A randomized, prospective trial. PARTICIPANTS: Thirty-one consecutive patients undergoing 49 cycles of controlled ovarian hyperstimulation/IUI were studied in a tertiary care setting. MAIN OUTCOME MEASURES: Ovulation was determined sonographically. The establishment of a clinical pregnancy was defined by either ultrasonographic verification of cardiac activity within an intrauterine fetus, or histologic confirmation of trophoblast in a surgical specimen. RESULTS: Clinical pregnancies developed in 2 of 23 cycles in the single insemination group, compared with 12 of the 23 cycles in the double insemination group. Cycle fecundity was significantly higher for group II (0.522) than for group I (0.087) patients (P = 0.003). CONCLUSION: In hMG/hCG cycles, two IUIs timed as described above are superior to one periovulatory insemination.     

Ovarian hyperstimulation syndrome: prediction by number and size of preovulatory ovarian follicles

Monitoring of human menopausal gonadotropin (hMG) treatment for induction of ovulation according to either preovulatory estrogen levels or the presence of a dominant ovarian follicle was found insufficient to prevent ovarian hyperstimulation syndrome (OHS). In 65 infertile patients treated with hMG and human chorionic gonadotropin (hCG), a possible correlation between the number and size of all ovarian follicles on the day of assumed ovulation and the occurrence of OHS was evaluated in order to assess the value of ultrasonography in predicting OHS. It was found that patients with OHS had significantly more follicles at the time of hCG than patients without OHS. Mild OHS was characterized by the presence of eight to nine follicles, 68.7% of which were of intermediate size (9 to 15 mm). In moderate to severe OHS 95% of the preovulatory follicles were less than 16 mm, most of them (54.7%) less than 9 mm in diameter. It can be concluded that a specific preovulatory follicular configuration characterizes mild and severe hyperstimulation. This is important information before hCG administration and emphasizes the value of ovarian ultrasonography in predicting OHS.     

Monitoring gonadotrophin therapy by real-time ultrasonic scanning of ovarian follicles

Real-time ultrasound scanning of ovarian follicles was performed during 61 cycles in 22 infertile patients being treated with sequential injections of human menopausal gonadotrophin (hMG) and human chorionic gonadotrophin (hCG). Total 24-h urinary oestrogens were estimated (and in 13 cycles plasma oestradiol) but the amount of gonadotrophin given was based mainly on the ultrasound findings. A retrospective analysis of the results showed that there was a poor statistical correlation between the diameter of the largest follicle and the total urinary oestrogens (r=0.39) and with the level of plasma oestradiol (r=0.56), although similar clinical information was obtained by all methods. Ovulation was induced in 58 cycles when the leading follicle had a mean diameter of 20-25 mm (mean 21.3 mm); follicular rupture was observed in 57 cycles and in these cases there was biochemical evidence of luteinization (plasma progesterone greater than 15 nmol/1; total urinary pregnanediol greater than 8 nmol/24h). Three patients (three cycles) were not given hCG; one developed micropolycystic ovaries and two showed evidence of hyperstimulation (one follicle greater than 25 mm diameter, three or more follicles 20-25 mm diameter). Twelve patients became pregnant, all with single fetuses. Subsequently one aborted, one had an ectopic pregnancy, three gave birth to normal babies at term and seven pregnancies are continuing. Real-time ultrasound scanning of ovarian follicles is a simple, practical method for monitoring follicular growth during the administration of hMG and predicting the response to hCG.     

Responses of patients to different lots of human menopausal gonadotropins during controlled ovarian hyperstimulation

Responses of patients treated with different lots of human menopausal gonadotropin (hMG) during controlled ovarian hyperstimulation were analyzed. Levels of luteinizing hormone (LH) in serum varied between groups of patients treated with different hMG lots, serum follicle-stimulating hormone (FSH) levels did not differ. In the analysis of levels of estradiol (E2) in serum of patients pretreated with leuprolide acetate (gonadotropin-releasing hormone analog; GnRH-a), there was an interaction between hMG lot and day of stimulation. E2 levels/follicle also diverged between hMG batches as ovum pick-up approached. Within the groups of patients pretreated with GnRH-a, serum FSH/LH ratios varied between 5 and 20, with a batch x day interaction. Ongoing pregnancy rates in the hMG-treatment groups ranged between 0/24 and 7/33 (21%).     

Controlled ovarian hyperstimulation for the new reproductive technologies

The aim of controlled ovarian hyperstimulation (COH) is to induce multiple morphologically and functionally adequate follicles with the aim of harvesting multiple fertilizable oocytes. We compared several treatment regimens with different FSH/LH ratios: group I was the basic 2 human menopausal gonadotropins (2hMG) protocol in which 2 ampules of hMG were administered starting on day 3 of the cycle; group II was the basic 2hMG in which 2 ampules of "pure" follicle stimulating hormone (p-FSH) were added on day 3 and 4; group III was the 2 FSH protocol in which 2 ampules of p-FSH were administered beginning on day 3; finally, group IV was the 4FSH: 4 ampules of p-FSH on day 3 and 4 followed by 2 ampules of p-FSH daily. The reference regimen was the 2hMG. Except for the higher rate of immature oocytes in 2FSH and 2hMG protocols, the number of preovulatory oocytes and fertilization rate were similar in all protocols. No differences occurred in the pregnancy outcome. The low dose Lupron (LDL) stimulation was an experimental protocol applied to two groups of women who had previously failed COH. Eight women who had a premature luteinization and 8 women who showed a low response agreed to participate in the protocol. Ten micrograms of the GnRH agonist leuprolide acetate (Lupron) were injected subcutaneously every 6 hours starting on cycle day 2 and menotropin stimulation was begun on day 3-5, according to individual patient response. The LDL protocol was successful in determining a favourable estradiol pattern and fertilizable oocytes.     

超声下未成熟卵泡抽吸术治疗多囊卵巢综合征不孕的临床研究

目的　探讨超声下未成熟卵泡抽吸术(IMFA)对多囊卵巢综合征(PCOS)不孕患者卵巢窦卵泡计数及其内分泌功能的影响;观察IMFA后,应用人绝经期促性腺激素(hMG)促排卵治疗的效果、妊娠及并发症情况。方法　将71例PCOS不孕患者随机分为两组。组Ⅰ: 37例,穿刺前用少量hMG促排卵; 组Ⅱ: 34例,不用任何促排卵药物。在阴道超声引导下进行IMFA,检查穿刺后第2个周期患者的内分泌功能和卵巢基础窦卵泡计数,可连续2~3个周期进行穿刺。随后2组均用hMG常规促排卵治疗,随访其排卵及妊娠情况。结果　组Ⅰ进行了88个周期的穿刺治疗,经过2~3次穿刺后,睾酮水平、黄体生成素(LH )与卵泡刺激素(FSH)的比值均明显降低,与治疗前比较,差异有统计学意义(P<0. 01), 33例(89%, 33 /38)患者基础窦卵泡计数降至10个/卵巢以下。组Ⅱ进行了87个周期治疗,所有患者睾酮水平均显著降低,与治疗前比较,差异有统计学意义(P<0 01 ); 30例LH/FSH<2, 28例(82%, 28 /34)患者基础窦卵泡计数降到10个/卵巢以下。在IMFA之后, 诱发排卵时hMG用量组Ⅰ为(21±6)支,组Ⅱ(23±10)支,两组比较,差异无统计学意义(P>0 .05),在注射人绒毛膜促性腺激素(hCG)后均出现排卵, 组Ⅱ有2例发生轻度卵巢过度刺激综合征(OHSS)。连续促排卵治疗1 ~3个月后, 共36例(51% )     

Follicular phase gonadotropin-releasing hormone agonist and human gonadotropins: a better alternative for ovulation induction in in vitro fertilization

Leuprolide acetate was used in 189 in vitro fertilization (IVF) cycles. Patients were allocated prospectively into two groups: In group A (96 cycles), leuprolide acetate was started on the 2nd menstrual cycle day of the actual IVF attempt. In group B (93 cycles), leuprolide acetate was started on the 3rd luteal phase day of the preceding IVF cycle. Ovulation was induced with a combination of pure follicle-stimulating hormone (FSH) and human menopausal gonadotropins (hMG), starting on or before the 5th cycle day, respectively. Leuprolide acetate and gonadotropins were continued until the day of human chorionic gonadotropin (hCG) administration. Follicular aspiration was carried out either by laparoscopy or by transvaginal ultrasound guidance. Group A required a lower number of FSH and hMG ampules than group B; nevertheless, there was no difference in the number of follicles, percentage of preovulatory oocytes or fertilization rate between the groups. The number of embryos transferred was 3.3 and 3.4, respectively. A significantly higher pregnancy rate was observed in group A (40.6% versus 27.7%) and a lower miscarriage rate (22.8% versus 36%) than in group B. In short, this study suggests that there is no need to administer leuprolide acetate routinely during the luteal phase of the preceding IVF cycle.     

Relationship of follicle number, serum estradiol level, and other factors to clinical pregnancy rate in gonadotropin-induced intrauterine insemination cycles

Objective:To determine the characteristics associated with clinical pregnancy rate after gonadotropin-induced intrauterine insemination cycles in patients without male or tubal factor infertility. Materials and methods:One hundred and eighty patients undergoing controlled ovarian hyperstimulation followed by intrauterine insemination were included in the study retrospectively. The patients’ files were retrospectively evaluated with respect to age, number of follicles, endometrial thickness and serum hormone levels at baseline and at the day of human chorionic gonadotropin (hCG) administration. The patients with male or unilateral tubal factor infertility were excluded from the study. Results:The serum estradiol level at the day of hCG administration was not correlated with the clinical pregnancy rate (r=–0.05, p=0.481). The number of follicles was not correlated with the clinical pregnancy rate (r=–0.09, p=0.209). There was no significant difference between the clinically pregnants (n=32) and not pregnants (n=148) regarding the mean age, baseline serum levels of luteinizing hormone (LH) and estradiol, serum estradiol and LH levels at the day of hCG administration and endometrial thickness (p>0.05). Although not statistically significant, a pregnancy rate of 14.2% with less than 3 follicles ≥18 mm is present compared to a pregnancy rate of 27.5% with at least 3 follicles ≥18 mm and 24% with ≥4 follicles ≥18 mm. Conclusion: The clinical pregnancy rate does not seem to be affected with the number of follicles present at the time of intrauterine insemination or the serum estradiol level at the day of hCG administration in a controlled ovarian hyperstimulation cycle in non-andrologic and non-peritubal factor infertility; however, there is a clear trend towards higher pregnancy rates with higher number of follicles. Received: 8 December 2000 / Accepted: 19 February 2001     

Effect of a gonadotropin-releasing hormone agonist and gonadotropins on ovarian follicles in cynomolgus monkey: a model for human ovarian hyperstimulation

STUDY OBJECTIVE: To examine the effect on large follicles (greater than or equal to 2 mm) of human menopausal gonadotropin (hMG) and buserelin acetate, a gonadotropin-releasing hormone agonist in monkeys. DESIGN: Experimental. SETTING: Reproductive research laboratory. ANIMALS: Fourteen cyclic cynomolgus monkeys receiving hMG alone for 8 days or buserelin acetate plus 8 (group 1), 12 (group 2), or 16 (group 3) days of hMG administration always starting from day 1 of the cycle. RESULTS: The different treatments were effective in over-riding the specific ovulatory quota of 1, and more large follicles developed in treatments involving long duration and higher doses of hMG. In buserelin acetate plus hMG treatments, the frequency of dissociated follicles and follicles in late atresia were, respectively, lower and higher than in hMG alone treatment. The numbers of recoverable mature oocytes (germinal vesicle breakdown) were similar to the numbers of such oocytes recovered after hyperstimulation performed for human in vitro fertilization and embryo transfer (IVF-ET). However, the number of mature oocytes enclosed in typically preovulatory follicles was very low because there were numerous dysmature follicles. CONCLUSION: These data suggest a deleterious effect of buserelin acetate plus hMG treatments on the recruitable follicles at the time when treatments start. The implications of these observations in the field of human IVF-ET are discussed.