The effect of insulin on in vitro progesterone production of human granulosa cells.

Insulin appears to play an important role in regulating ovarian function in some mammals. The present study assessed the effect of insulin on progesterone production by human granulosa lutein (G-L) cells in vitro. G-L cells were isolated from individual follicles at the time of laparoscopy for oocyte retrieval in patients undergoing in vitro fertilization/embryo transfer (IVF/ET). G-L cells were purified and plated for culture. Control wells contained no additions, while insulin was added to test wells. Although G-L cells obtained from follicles which contain an oocyte that subsequently fertilizes in vitro produce more progesterone at three and six days of culture than G-L cells from follicles that contain an oocyte that does not fertilize in vitro, insulin is unable to increase further the progesterone production of G-L cells from follicles containing either fertilized or nonfertilized oocytes at days 3 and 6 in culture. Further analysis based on the stimulation protocol (follicle stimulating hormone, n = 13; clomiphene citrate/hMG, n = 19; hMG, n = 10) also failed to yield a significant difference in basal or insulin-stimulated progesterone secretion after three or six days in culture. The lack of an effect of insulin on progesterone production by G-L cells in vitro may indicate that these cells are maximally stimulated following hyperstimulation and cannot increase progesterone production further, or may signify that insulin has no effect on the in vitro luteinization of human G-L cells obtained from hyperstimulated cycles.     

Alteration of human follicular fluid plasminogen activator activity by ovarian hyperstimulation

Recently, it has been shown that granulosa-cell secretion of plasminogen activator (PA) is responsive to luteinizing hormone (LH)/human chorionic gonadotropin (hCG) as well as follicle stimulating hormone (FSH) in the rat and the pig. Accordingly, we asked whether PA activity in follicular fluid from exogenously stimulated human follicles was different from that of normal cycles and whether or not these activities correlated with follicular maturation as determined by follicular fluid steroid concentration. Follicular aspirates were obtained from women who were participating in an in vitro fertilization protocol. Follicular fluid concentrations of estradiol and progesterone were determined by established radioimmunoassay. PA activity, determined using a modified indirect solid-phase radioassay, was significantly less in follicles from patients treated with human menopausal gonadotropin (hMG) plus clomiphene (P<0.05) compared to untreated patients or those receiving hMG or clomiphene alone. Correlations of PA activity and follicular fluid steroid concentrations demonstrated no significant correlation in samples from treated patients. In contrast, untreated spontaneously cycling patients had a significant (r=0.89,P<0.05), positive correlation between follicular fluid estradiol levels. There was no correlation between PA activity and follicular fluid progesterone levels in any of the groups. These results suggest that a subtle balance in granulosa-cell secretion of PA and steroids exists, which appears to be disrupted by follicular hyperstimulation during treatment of patients participating in in vitro fertilization protocols.Supported in part by Clinical Investigator Award HD-00401 and by the University of Southern California Faculty Research and Innovation Award.     

Levels of steroid and protein hormones in antral fluids of women treated with different combinations of gonadotropins, clomiphene citrate, and a gonadotropin-releasing hormone analog

Levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, progesterone (P), and total protein in follicular fluids collected from 18 patients pretreated with a gonadotropin-releasing hormone analog (GnRHa), in association with human menopausal gonadotropin (hMG) and FSH, were compared with values for 69 patients treated with FSH, hMG, FSH/hMG, or clomiphene citrate (CC)/hMG in an in vitro fertilization (IVF) program. The authors have established a number of significant differences in chemical and physical properties of follicular fluids of patients treated by different regimen, and concur with earlier evidence that the volume of a follicle, and its P and total protein content, are related to the maturity of the oocyte nested within the follicle. Overall, however, differences in concentrations of gonadotropins in follicular fluids between groups were not consistent with differences in follicular fluid steroid levels, and levels of immunoactive gonadotropins in follicular fluids were not in accord with dosages of exogenous immunoactive gonadotropin administered during hyperstimulation. The most favorable outcomes of IVF (greater than 70% of oocytes fertilized) were established with oocytes collected from patients treated with FSH only or with CC/hMG, and patients treated with FSH only yielded the highest average number of oocytes which fertilized in vitro (6.2 per patient).     

Oral contraceptive pills and follicular fluid hormones in an in vitro fertilization program

Fluids were collected from 136 ovarian follicles of 35 women undergoing in vitro fertilization and embryo transfer (IVF-ET). Fifteen women (76 follicles) received oral contraceptive pills (OCs) prior to ovulation induction. All women received human menopausal gonadotropins (hMG) for ovulation induction and in all cases follicular aspiration was performed 32 to 34 hours after an injection of human chorionic gonadotropin (hCG). The concentrations of follicular-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), and 17 beta-estradiol (E2) in the follicular fluids (FF) were measured by radioimmunoassay (RIA). FSH concentration in the FF of the OCs group (15 women, 76 follicles) was significantly lower (2.1 mIU/mL) as compared to the FSH (15.9 mIU/mL) in the FF of the control group (20 women, 60 follicles). The LH FF concentrations after hCG injection were similar in the two groups. The E2/P ratio in the OCs group (9.6) was significantly lower than the E2/P ratio in the control group (20.6). OCs given to patients before induction of ovulation with hMG results in lower E2/P ratios and lower FSH concentration in the FF.     

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.     

Serum steroids concentration might be used for monitoring the growth of follicles in friendly in vitro fertilization

Background:  Steroid levels have been used as the predictive parameters for oocyte maturation and embryo development. In the present study, estradiol and progesterone concentrations in the follicular fluid and serum were evaluated in conventional in vitro fertilization (IVF; follicle stimulating hormone [FSH] and/or human menopausal gonadotropin [hMG] after pituitary desensitization) and friendly IVF (no stimulation, clomiphene citrate, small dose of FSH or hMG without pituitary desensitization). The purpose of the present study was to evaluate the differences in steroid distribution between conventional and friendly IVF.
Methods:  Concentrations of estradiol, progesterone, FSH, and luteinizing hormone (LH) in serum and follicular fluid were determined in conventional and friendly IVF protocols by an enzyme-linked immunosorbent assay kit. Correlations between follicular fluid and serum steroid concentrations in these different protocols, and between pregnant cycles and steroid concentrations were evaluated.
Results:  Two hundred and thirty-four samples of follicular fluid from 74 IVF patients were analyzed. In conventional IVF, there was no relationship in steroid levels in between follicular fluid and serum steroids, whereas serum steroid concentrations correlated with the number of developing follicles. There was a relationship between the serum and follicular fluid estradiol levels ( r  = 0.467, P  < 0.0001) as well as progesterone levels ( r  = 0.227, P  = 0.0488) from friendly IVF patients.
Conclusions:  Serum steroid concentrations were mainly associated with the number of developing follicles. In the cases of friendly IVF, which had a small number of developing follicles, serum steroids might be used to monitor follicular fluid steroid concentrations. (Reprod Med Biol 2006; 5 : 277–282)     

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.     

Preovulatory follicular fluid steroid levels in stimulated and unstimulated cycles triggered with human chorionic gonadotropin

The purpose of this study was to analyze follicular fluid (FF) samples for steroid levels from stimulated and unstimulated cycles triggered with human chorionic gonadotropin (hCG) and to assess the influence of controlled ovarian hyperstimulation and luteinizing hormone/hCG on these levels. Spontaneous ovulatory cycles were monitored with serial ultrasound examinations, and hCG 10,000 IU was given when the lead follicle was mature. Fourteen FF samples yielding fertilizable oocytes were compared with 13 FF samples from controlled ovarian hyperstimulation cycles. Progesterone (P) was higher in controlled ovarian hyperstimulation than in unstimulated cycles (9.0 +/- 1.2 micrograms/mL versus 4.4 +/- 0.6 microgram/mL; mean +/- SEM), whereas estradiol (E2) was lower (0.8 +/- 0.1 microgram/mL versus 1.3 +/- 0.2 microgram/mL), resulting in a higher P:E2 ratio (15.5 +/- 3.3 versus 4.4 +/- 0.7). Androstenedione (A), testosterone (T), and T:E2 ratios were all higher in unstimulated than controlled ovarian hyperstimulation cycles. We conclude that controlled ovarian hyperstimulation is associated with increased FF P, decreased FF E2, T, and A levels, and decreased T:E2 ratios, suggesting altered steroidogenesis and enhanced follicular aromatase activity.     

Serum and follicular fluid (FF) estradiol (E2) levels in ovarian hyperstimulation syndrome (OHSS) during in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT) conception cycles after pituitary suppression

Initaial hope that ovarian hyperstimulation syndrome (OHSS) would be less likely to occur after pituitary suppression with gonadotropin releasing-hormone agonists (GnRH-a) has not been substantiated. GnRH-alhuman menopausal gonadotropin (hMG) protocols often lead to OHSS with markedly elevated circulating estradiol (E₂) levels in susceptible patients. This study was undertaken to determine whether or not intrafollicular E₂ secretion is increased in these cases. Fifty-two in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT) conception cycles treated with GnRH-alhMG were included in the study. GnRH-a, leuprolide, 0.5 mg, was administered subcutaneously from day 20 of the preceding cycle and the ovaries were stimulated with hMG, 75-225 IU bid intramuscularly, followed by human chrionic gonadotropin (hCG), 5000 IU. Twenty cycles (Group I) were associated with moderate or severe OHSS and 32 cycles (Group II) did not result in OHSS. E₂ was measured in the serum on the day of hCG (day 0), on the day of oocyte retrieval (day 2), and at midluteal phase (days 6–8), as well as in the follicular fluid (FF) using a solid-phase direct RIA. Mean serum E₂ was significantly higher at all three sampling times in Group I (OHSS) than in Group II. Both the number of follicles and the number of oocytes were also significantly higher in Group I. Mean (±SD) FF E₂ concentrations in both groups were similar (367±109 and 364±188) in follicles >15 mm in diameter but were increased in follicles 15 mm in diameter in OHSS (479±111) versus non-OHSS (230±32) patients. It appeared that OHSS was a function of an increased number of stimulated follicles as well as a result of altered steroidogenic function at the follicular level.     

Comparison of follicular fluid hormones in patients with one or two ovaries participating in a program of in vitro fertilization

The authors recently reported on the follicular response to clomiphene citrate (CC) and human menopausal gonadotropins (hMG) in patients with one or two ovaries participating in a program of in vitro fertilization. This study was designed to analyze the follicular fluid hormones in patients with one or two ovaries in order to elucidate the compensatory mechanisms by which a single ovary achieves folliculogenesis equal to that of two ovaries. Twenty-one follicles from ten patients with one ovary were compared to 30 follicles from eight patients with two ovaries present. Ovulation induction was achieved using a standard protocol with sequential CC and hMG. Human chorionic gonadotropin (hCG) was administered after appropriate estradiol (E2) values and ultrasonic findings, and oocyte aspiration by laparoscopy was performed 33 hours later. Follicular fluid (FF) hormones were assayed by standard radioimmunoassay techniques and no differences were found in the levels of progesterone (P), testosterone, estradiol/testosterone ratio, prolactin, follicle-stimulating hormone, and luteinizing hormone. However, follicles from patients with one ovary had a lower mean concentration of E2 (286 versus 542 ng/ml, P = 0.001) and a lower mean E2/P ratio (0.055 versus 0.107, P = 0.016). Also, the mean follicular diameters and volumes were similar in both groups. In view of the authors' previous finding of a comparable number of mature oocytes from patients with either one or two ovaries, these data suggest that follicles from patients with a single ovary may achieve comparable oocyte maturity despite less efficient production of E2. Although FF E2 levels were lower in patients with one ovary, this dysynchrony between oocyte maturity and FF E2 values does not appear to affect outcome adversely.     

Ovarian stimulation with pure follicle-stimulating hormone/human menopausal gonadotropin and improved laparoscopic aspiration needles influence the success of an in vitro fertilization program

The effect of a combined pure follicle-stimulating hormone/human menopausal gonadotropin (pFSH/hMG) ovarian stimulation regimen and modified, sharpened laparoscopic follicular aspiration needles on the number of oocytes retrieved and the oocyte/follicle ratio in 43 consecutive cycles of in vitro fertilization (IVF) were retrospectively compared with 99 consecutive preceeding cycles stimulated with hMG alone and captured with aspiration needles that had never been sharpened. A modified laparoscopic follicular aspiration needle is described. Purified FSH/hMG ovarian stimulation significantly improved the mean serum estradiol levels, number of preovulatory follicles, and, therefore, the total number of oocytes recovered per cycle. The mean ratios of oocytes recovered per preovulatory follicle documented on ultrasound, and per aspirated follicle, increased significantly using sharpened needles. Both modifications improved the success rate of our IVF program.     

Comparison of maturation, meiotic competence, and chromosome aneuploidy of oocytes derived from two protocols for in vitro culture of mouse secondary follicles

PURPOSE: To compare maturation rates of mouse preantral follicles cultured using two previously reported follicle in vitro follicle culture protocols, and to compare the aneuploidy of oocytes derived from the two protocols with in vivo-matured control oocytes. METHODS: Mouse preantral follicles were either mechanically isolated then cultured in individual microdroplets, or enzymatically isolated and cultured in groups in a modified culture medium. Maturation of the follicles/oocytes and resulting oocyte aneuploidy rates were evaluated and compared. RESULTS: The mechanical isolation and individual culture protocol (M/I) resulted in higher follicle survival than the enzymatic isolation and group culture protocol (E/G) (89.1% versus 79.1%, p < 0.01), and better maturation to the metaphase 2 stage (61.5% versus 39.5%, p = 0.01) The rate of aneuploidy of oocytes not significantly higher in oocytes from the E/G group than the M/I group (15.4% versus 9.9%), but hypoploidy was significantly increased (4.7% versus 0.9%, p < 0.05). Both groups had a higher rate of aneuploidy than the control oocytes (2.9%, p < 0.02). CONCLUSIONS: These results indicate an increased survival and competency of oocytes derived from the M/I protocol, compared to the E/G protocol. The data highlight an increased susceptibility to meiotic errors in early stage follicles undergoing in vitro culture, compared to in vivo-matured oocytes.     

Follicular size and steroid secretion of dominant bovine follicles

Twenty one estrogen-active bovine follicles obtained in the preovulatory period prior to the endogenous LH peak were superfused for 10h. Follicular diameter and superfusate estradiol (E2), testosterone (T) and progesterone (P4) were measured. A close correlation between follicle size and E2 secreted into the superfusate was found (r = 0.77; p less than 0.01). There was no correlation between superfusate T or P4 and follicular diameter. These data indicate that within certain limits the amount of E2 secreted can be predicted by follicle size in an in vitro superfusion system. As follicle size correlates closely with granulosa cell number in estrogen-active follicles, one can speculate that the rise in estrogen secretion is a reflection of an increase in granulosa cell number of the dominant bovine follicle. The application of these in vitro findings to the in vivo situation might help in the interpretation of the quality of ovarian stimulation with hMG/hCG.     

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。     

Evidence for the production of a nonsteroidal endotheliotropic factor by human granulosa cells in culture.

OBJECTIVE: To determine the cellular source of the angiogenic activity displayed by follicular fluid (FF). DESIGN: Human granulosa cells were harvested from 27 follicular aspirates obtained 34 to 36 hours after eight patients, previously treated with human menopausal gonadotropin (hMG), follicle-stimulating hormone plus hMG, or clomiphene citrate and hMG received human chorionic gonadotropin (10,000 IU intramuscularly). Granulosa cells from individual follicles were plated at 50,000 cells/cm2 in Medium 199 (Sigma, St. Louis, MO) supplemented with either 5% calf serum or 0.1% bovine serum albumin; media collected 24 hours later was assayed in vitro measuring endothelial cell migration. Fractions depleted of steroids by reversed phase C1 chromatography were assayed as well. RESULTS: Granulosa cell-conditioned media from 18 of 27 follicles significantly stimulated endothelial cell migration (P less than 0.05). Chemoattractant activity did not appear to be related to steroid accumulation in the media and was not diminished in steroid depleted fractions. CONCLUSIONS: These findings suggest that human granulosa cells are a source of (nonsteroidal) endotheliotropic-angiogenic activity in FF.     

Combination clomiphene citrate/human menopausal gonadotropin stimulation protocols for in vitro fertilization-embryo transfer

Various protocols have been utilized for stimulation of multiple ovarian follicles in patients undergoing in vitro fertilization-embryo transfer (IVF-ET). Previous studies have suggested that the combination of clomiphene citrate (CC) and human menopausal gonadotropins (hMG) is superior to either CC or hMG alone in terms of follicular development, oocyte recovery, and embryo transfer. However, no significant increase in viable pregnancy rates has been reported with any of the protocols. This report examines five different CC/hMG protocols. While differences were seen in terms of serum estradiol response and fertilization rates of mature oocytes among the various protocols, no significant differences were found in terms of follicular development, oocyte recovery, embryo transfer, or pregnancy. The pregnancy rate in IVF-ET appears unaffected by variations in the dose and timing of CC and hMG in a combination protocol.     

IVF中三种促超排卵方案效果的比较

目的：探讨IVF中最佳促超排卵方案。方法：将IVF对象随机分为3组。BFh组：23例126个周期,按BFh长方案（Buserelin／FSH／hCG）进行;Chh组：13例14个周期,以CC／hMG／hCG方案进行;Fhh组：55例57个周期,按FSH／hMG／hCG方案进行。结果：每周期平均促性腺激素（Gn）用量BFh组为18．62±5．95支;Chh组16．57±5．70支;Fhh组25．56±8．08支。每周期获成熟卵子数分别为10．23±5．80个;6．07±3．22个;10．96±6．45个。Gn用量BFh组与Chh组差异无显著性（P＞0．05）,但取到的卵子数,差异有显著性（P＜0．05）。BFh组与Fhh组比较,BFh组Gn用量少于Fhh组（P＜0．05）,但取到的卵子数差异无显著性（P＞0．05）,且BFh组无过早的LH峰出现,另二组则各有1例过早的出现内源性LH峰。结论：IVF中BFh方案是较为理想的促起排卵方案。     

Effects of recombinant human FSH (rhFSH), urinary purified FSH (uFSH), and hMG on small preantral follicles and tertiary follicles from normal adult and androgen-sterilized female mice

OBJECTIVE: To examine the stage-specific follicular response to recombinant human FSH (rhFSH), urinary FSH (uFSH), and hMG preparations. SETTING: In vitro follicle culture. INTERVENTION(S): Small preantral and tertiary follicles isolated from adult normal BDF-1 mice and androgen-sterilized mice were cultured with rhFSH, uFSH, and hMG for 4 days. MAIN OUTCOME MEASURE(S): Follicular diameter. Immunoreactive inhibin, E2, and progesterone concentrations in cultured medium. RESULT(S): The minimal effective dose of rhFSH, uFSH, and hMG for the follicular growth of small preantral follicles from normal mice was 10 mIU/mL, 1 mIU/mL, and 0.1 mIU/mL, respectively. For tertiary follicles from normal mice, the minimal effective dose of rhFSH, uFSH, and hMG was 10 mIU/mL, 10 mIU/mL, and 1 mIU/mL, respectively. The minimal effective dose of hMG for the follicular growth of small preantral follicles from androgen-sterilized mice was 0.01 mIU/mL, and that of rhFSH and uFSH on tertiary follicles from androgen-sterilized mice was 1 mIU/mL and 10 mIU/mL, respectively. No significant increase was found in the follicular diameter of the tertiary follicles from androgen-sterilized mice as a result of stimulation by hMG, but an hMG dose of >10 mIU/mL produced a significant increase in progesterone secretion. CONCLUSION(S): Human menopausal gonadotropin preparation acts detrimentally on follicles from androgen-sterilized mice by increasing the sensitivity of small preantral follicles to FSH and by inducing the luteinization of tertiary follicles.     

Reduction of dehydroepiandrosterone sulfate synthesis in women with polycystic ovary syndrome by human menopausal gonadotropin but not purified urinary follicle stimulating hormone: a comparative pilot study.

We aimed to compare the effects of two different gonadotropins on steroid production in patients with polycystic ovary syndrome (PCOS). The study group comprised 20 infertile patients diagnosed with PCOS who were accepted into in vitro fertilization-embryo transfer and gamete intra-Fallopian transfer programs. Ten patients were consecutively allocated to a purified urinary follicle stimulating hormone (FSH) administration group while the other ten received human menopausal gonadotropin (hMG). All patients were pretreated with a gonadotropin releasing hormone-agonist. The patients were followed by daily vaginal ultrasonography until at least two follicles reached a diameter of 17 mm or an estradiol value of at least 100 pg/ml per follicle. To induce ovulation, human chorionic gonadotropin was given. On the 3rd day of menstruation, serum estradiol, luteinizing hormone (LH), FSH, total testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), insulin-like growth factor-I and insulin were measured. These same parameters were measured again on the day of follicle aspiration in both serum and follicular fluid. In both groups, the serum levels of estradiol and androstenedione were raised significantly, and on aspiration day the serum level of DHEAS was significantly raised in the FSH group but not in the hMG group. Our findings suggest that in PCOS patients exogenous hMG induces a different steroid synthesis pattern compared to pure FSH, hypothetically by reduction of the delta-5 steroid synthesis pathway in the adrenals and/or in the ovary.     

Treatment of clomiphene citrate-resistant polycystic ovarian syndrome with pure follicle-stimulating hormone or human menopausal gonadotropin

Two hundred ten treatment cycles of follicle-stimulating hormone (FSH) or human menopausal gonadotropin (hMG) were completed in 49 patients with clomiphene citrate-resistant polycystic ovarian syndrome. The results from 68 cycles of daily intramuscular (IM) FSH and 41 cycles of IM hMG were compared. The ovulation rate, maximum serum estradiol (E2) levels achieved, and pregnancy rate were similar in both groups, but FSH resulted in significantly fewer follicles developing and hyperstimulation. The 68 cycles of daily IM FSH were further compared with the outcome of administering the FSH as an alternate-day IM injection in 70 cycles, and by subcutaneous pulsatile injection in 31 cycles. There were no differences in any of the parameters measured between daily and alternate-day FSH. Pulsatile FSH required a greater total dose over a longer period of time to achieve stimulation. It also produced fewer follicles, a lower maximum serum E2 level, and the lowest incidence of hyperstimulation. Twenty pregnancies resulted, of which 6 aborted in the first trimester; there was 1 set of twins and 13 singleton pregnancies. The cumulative pregnancy rate after 6 treatment cycles was 62%.