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.     

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.     

Simplification of the method of in vitro fertilization: Sonographic measurements of follicular diameter as the sole index of follicular maturity

As a simplification of the in vitro fertilization (IVF) procedure, repeated sonographic scanning of follicular diameters in stimulated cycles was performed, until the largest visible follicle reached a mean diameter of at least 28 mm, at which time human chorionic gonadotropin (hCG) was administered. Follicle puncture was performed either guided by sonography or by laparoscopy 34–36 hr after the hCG injection, and following insemination oocytes were cultured for 48–60 hr before embryo transfer (ET). Serum levels of luteinizing hormone (LH), prolactin (PRL), and estradiol-17 (E₂) at the time of hCG injection as well as follicular fluid levels of follicle stimulating hormone (FSH), LH, and PRL as well as progesterone (P), testosterone (T), and E₂ at the time of puncture were determined in retrospect using specific radioimmunoassay (RIA). It was found that the knowledge of a single value of LH or E₂ in serum should have been of little additional value for the decision to give hCG in all stimulation models used: clomiphene+hCG, human menopausal gonadotropin (hMG)+hCG, and clomiphene+hMG+hCG. The concentrations of the three steroids measured in follicular fluid were, in a high proportion of the follicles, within a normal range in all stimulation models. The group receiving clomiphene+hMG+hCG appeared promising through its higher proportion of estrogenic follicles. It is concluded that sonographic measurement of follicular diameters may be used as the sole index of follicular maturity in an IVF program. In cases with more pronounced superovulation as may be obtained by hMG stimulation, serial E₂ analyses are required in addition in order to ensure a high proportion of estrogenic follicles and an optimal pregnancy rate.     

Spontaneous luteinizing hormone (LH) surges are associated with more rapidly increasing estradiol (E2) and follicle stimulating hormone (FSH) in in vitro fertilization and embryo transfer

In a retrospective analysis of 64 patients stimulated with human menopausal gonadotropin (hMG) and/or pure follicle stimulating hormone (FSH); 35 cycles with spontaneous luteinizing hormone (LH) surges were compared with 29 control cycles with respect to serum FSH and estradiol (E₂) levels drawn on the day prior to and the day of human chorionic gonadotropin (hCG), approximately 16 hr after gonadotropin stimulation. FSH decreased significantly (P<0.05) in control cycles where two or more preovulatory oocytes (preovs) were obtained, in contrast to cycles with a spontaneous LH surge, where FSH increased irrespective of the number of preovs. The E₂ increase in the LH surge cycles was significantly higher (P<0.05) than in the control cycles. However, the increase in E₂ did not correlate with the change in FSH levels or with the number of preovs.     

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.     

Increased human menopausal gonadotropin dose during the early follicular phase: Effect on follicular recruitment and treatment outcome

Summary To investigate whether the provision of increased gonadotropins would enhance follicular recruitment and selection, women not responding (N=18) to our standard clomiphene citrate (CC)-human menopausal gonadotropin (hMG) regimen were treated with increased hMG (treatment cycle II). Estradiol levels were higher in treatment cycle II and these differences were significant on days 8 and 9 (P0.05 andP0.03, respectively). On day 9, better follicular development was seen in cycle II (P0.05). While none of the patients responded in cycle I, 10 of 18 responded in cycle II. Of the 10 responders, 2 conceived following in vitro fertilization and embryo placement. Increasing the dose of hMG improved the development of a cohort of follicles so that aspiration and possible pregnancy were achieved in women who were previously unresponsive to therapy.     

A randomized prospective study on the effect of short and long Buserelin treatment in women with repeated unsuccessful in vitro fertilization (IVF) cycles due to inadequate ovarian response

Fifty four women with repeated unsuccessful in vitro fertilization (IVF) cycles due to inadequate ovarian response to stimulation with human menopausal gonadotropins (hMG) participated in this study. They were randomized to receive either gonadotropin releasing hormone agonist (GNRHa), Buserelin, prior to and during induction of ovulation by hMG (Group I—long protocol), or GnRHa starting on the first day of the cycle together with induction of ovulation by hMG (Group II—short protocol). Mean follicular phase serum luteinizing hormone (LH) and progesterone (P) levels were significantly lower in Group I than in Group II (P<0.01). Cancellation rate was significantly lower in Group I than in Group II (P<0.01). The long GNRHa protocol resulted in statistically significant lower cancellation rates, more oocytes per pickup (OPU), more embryos trans-ferred per patient, and a higher pregnancy rate. Significantly more hMG ampoules and more treatments days were required in the long GNRHa protocol. Our data demonstrate that the use of GNRHa prior to and during ovarian stimulation with hMG offers a very good alternative for patients with repetitive unsuccessful IVF cycles due to inadequate response.     

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% )     

The use of ovarian ultrasonography in monitoring ovulation induction

Ovarian ultrasonography is a new diagnostic technique which has become almost essential in monitoring ovulation. Recent improvements in ultrasound technology have allowed for accurate assessment of the number and size of the developing follicles and their rate of growth, as well as ovulation and postovulatory events. In the non-stimulated cycle follicular size correlates well with optimal maturation and there is a linear correlation between follicular diameter and plesma estradiol (E₂ levels). In stimulated cycles, because of asynchrony of various recruited coliorts of follicles, these rules are not as steadfast, These observations indicate that when there is endogenous gonadotropic activity, follicular growth stimulated by human menopausal gonadotropins (hMG) does not develop synchronously. The aim should be, therefore, not only to improve the monitoring system but mainly to synchronize the cohorts of follicles recruited for development in any one cycle by a better regimen for ovalation induction. In view of the high success rate of hMG treatment in patients without endogenous gonadotropin secretion, it is tempting to speculate that inducing similar conditions in women with endogenous gonadotropin production may have a significant change in the pattern of follicular development in their conception rate.     

Antiestrogenic effect of clomiphene citrate in a multiple follicular stimulation protocol

End-organ antiestrogenic effects of clomiphene citrate (CC) have been demonstrated in the female reproductive tract at the levels of the ovary, cervix, and endometrium. However, it has not been established whether this effect is manifested during concomitant human menopausal gonadotropin (hMG) administration, as occurs in hMG/ CC stimulations of multiple follicular development. To assess this question a review was made of serum estradiol (E₂) and cervical mucus in 47 hMG and 56 hMG/CC stimulations on days-2,-1,0, and+1 relative to the day of hCG administration. E₂ levels (pg/ml) were significantly lower in the hMG as compared to the hMG/CC group. However, comparing the hMG and hMG/CC groups, cervical mucus scores were significantly higher in the former. Furthermore, an analysis of covariance demonstrated that the cervical mucus scores on each day were significantly lower in the hMG/CC group (P<0.001). Thus, in hMG/CC stimulations for in vitro fertilization (IVF), despite the concomitant administration of pharmacologic doses of hMG, CC exerts an antiestrogenic effect on at least one end organ, cervical mucus production. Potentially, this antiestrogenic effect in IVF stimulations would be exerted at other female reproductive tract sites including the endometrium; however, its clinical significance, if any, is unclear.     

Relationship among serum levels of luteinizing hormone,estradiol, and progesterone during follicle stimulation and results of in vitro fertilization and embryo transfer (IVF-ET)

Eighty-eight IVF-ET cycles were classified into four groups according to the results of IVF-ET (Group A—conceptional cycles, 10 cycles; Group B—cycles with cleaved oocytes, 58 cycles; Group C—cycles with fertilized oocytes, 9 cycles; Group D—cycles without fertilization, 11 cycles). Serum luteinizing hormone (LH), estradiol (E ₂ ), and progesterone (P) levels during follicle stimulation were studied in these groups. Patients participated in our IVF-ET program due to irreparable tubal damage. Follicle development was stimulated with a clomiphene—human menopausal gonadotropin (hMG)—human chorionic gonadotropin (hCG) regimen. Group C showed a low E ₂ response to follicle stimulation. Groups B and D showed significantly higher serum P levels on day 0 (the day of hCG injection) than Group A (Group A, 0.73 ± 0.11, vs Groups B and D, 1.43 ± 0.15 and 2.17 ± 0.42 ng/ml; P <0.01). The effects of serum P and LH levels on the fertilization and pregnancy rates were studied. The pregnancy rate was not affected by the serum LH level but was only 2.7% in cycles in which serum P was 1.2 ng/ml on day 0, which was significantly lower than that in cycles in which serum P was <1.2 ng/ml on day 0 (19.1%) (P <0.05). The fertilization rate was significantly lower in the cycles with higher levels of serum P and/or LH than in cycles in which serum P was <1.2 ng/ml and serum LH was normal (50.5 vs 78.8%; P <0.01). These findings suggest that the serum P level, but not the LH level, during follicle stimulation is closely related to the achievement of pregnancy.     

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.     

Induction of ovulation in amenorrheic patients with gonadotropin-releasing hormone and human menopausal gonadotropin

In five hypothalamic amenorrhea patients who underwent chronic intermittent gonadotropin-releasing hormone (GnRH) therapy for induction of ovulation, small doses (2 to 4 ampules/day) of human menopausal gonadotropin (hMG) were administered 9 to 32 days after the start of GnRH treatment. In seven treatment cycles, the addition of hMG initiated a sudden rise of 17 beta-estradiol concentrations, followed by a luteinizing hormone and follicle-stimulating hormone surge and ultrasonographic evidences of ovulation. Four of five patients conceived (singleton pregnancies) after the first or second treatment course. There were no clinical signs of ovarian hyperstimulation. Combined therapy of GnRH and hMG may be useful, therefore, for the treatment of hypothalamic amenorrhea patients who demonstrate prolonged follicular phases or luteinized unruptured follicle syndrome under chronic treatment with pulsatile GnRH alone.     

Absence of effect of adjuvant growth hormone therapy on follicular responses to exogenous gonadotropins in women: normal and poor responders.

OBJECTIVE: To examine the effects of growth hormone (GH) on ovarian responses to exogenous gonadotropins after pituitary desensitization in normal and poor responder patients undergoing in vitro fertilization. DESIGN: A prospective study with comparison of control and GH-treated cycles. PATIENTS: Poor responder patients (n = 10) required > 44 ampules of human menopausal gonadotropin (hMG) to achieve criteria for administration of human chorionic gonadotropin (hCG) on day 0 or cancellation in control cycles, and normal responder patients (n = 10) required < 45 ampules. MAIN OUTCOME MEASURES: Ovarian responses to hMG assessed by duration of stimulation required to achieve first significant estradiol (E2) response and hCG criteria. Total doses and duration of hMG, follicular development and E2 concentrations on day 0, and embryology were also assessed. RESULTS: Growth hormone showed no effect on any of the parameters studied in either patient group. CONCLUSION: Follicular recruitment, E2 secretion by mature follicles, and oocyte yield and quality were uninfluenced by GH treatment.     

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 Δ-5 steroid synthesis pathway in the adrenals and/or in the ovary.     

Inhibin activity of preovulatory follicles of gonadotropin-treated and untreated women

In order to determine whether treatment of endocrinologically normal women with human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) led to alternations in follicular fluid inhibin activity and steroids, both inhibin activity and steroid levels were measured in follicular fluid of 10 follicles of 9 women treated with hMG/hCG and in follicular fluid of 15 preovulatory follicles of 15 untreated women. The women were given 150 IU hMG daily from day 3 until the serum estrogen levels were greater than 300 pg/ml, at which time hMG was discontinued and 10,000 IU hCG was given 50 hours later. Follicular fluid was aspirated from all visible follicles 36 hours after hCG. Women treated with hMG/hCG had multiple (two to five) follicles containing 1.5 to 4.5 ml of follicular fluid and a mature oocyte and elevated serum estrogen (400 to 800 pg/ml) on the day after hCG treatment. At the time of follicular fluid recovery, there was more inhibin activity (204 +/- 14 U/10 ml) in the hMG/hCG-stimulated follicles than in unstimulated follicles of a control group of women (65 +/- 14, mean +/- standard error, P less than 0.05). Follicular fluid from follicles of hMG/hCG-treated women had lower estrogen and progesterone levels, compared with normal preovulatory women. These data show that treatment of patients with hMG/hCG is associated with elevated follicular fluid inhibin activity.     

Relationship between the steroid and prolactin concentration in follicular fluid and the maturation and fertilizaton of human oocytes

Seventyeight follicles and their follicular fluid were aspirated from 46 women undergoing in vitro fertilization (IVF) procedures after stimulation of the ovaries with a low-dose human menopausal gonadotropin/human chorionic gonadotropin stimulation regimen. The concentrations of estradiol (E₂), progesterone (P), testosterone (T), and prolactin (PRL) were measured in follicular fluid and related to the maturation of the oocyte-corona-cumulus complex (OCCC) and the fertilization of oocytes. Follicles containing mature oocytes had significantly higher follicular fluid E₂ and P levels than follicles with intermediate and immature oocytes. A constant decrease in PRL and T values with advancing follicular maturation was observed. Similar results were obtained when the fertilizing ability of the oocytes was examined. The gradual decline in follicular fluid PRL and T levels during follicular development was connected with increasing E₂ and P biosynthesis and therefore seems to be an important precondition for normal follicular and oocyte maturation.     

Evaluation of two gonadotropin-releasing hormone (GnRH) analogues (leuprolide and buserelin) in short and long protocols for assisted reproduction techniques

Purpose The administration of two GnRH analogues (buserelin and leuprolide acetate) in long and short protocols was evaluated prospectively. In the long protocol, the analogues were given from day 1 of the cycle for at least 14 days and then hMG administration was started, while in the short protocol the analogues were initiated from cycle day 1, adding hMG from day 3. The patients were divided into four groups according to the protocol used: Group I, buserelin-long; Group II, buserelin-short; Group III, leuprolide-long; and Group IV, leuprolide-short. Serum E ₂ levels on the day of hCG injection and the number of follicles observed, oocytes retrieved, and embryos obtained, as well as implantation rates, were significantly higher (P<0.001) in the long protocols than in the short ones.Results Pregnancy rates were similar in all groups, although a trend for better results was observed in buserelin-long compared to buserelin-short. There were no differences in the results achieved with buserelin or leuprolide.Conclusion The administration of GnRH analogues (buserelin and leuprolide acetate) in long protocols induced a more intense ovarian response and was associated with significantly higher implantation rates and also a trend for higher pregnancy rates, although this difference was not statistically significant.     

多囊卵巢综合征伴催乳素水平升高不孕患者的药物治疗效果分析

目的 探讨多囊卵巢综合征(PCOS)伴催乳素水平升高不孕患者的药物治疗方案及效果.方法 回顾性分析2005年1月至2007年3月在山东大学附属省立医院生殖医学中心就诊的PCOS伴催乳素水平升高不孕患者63例.根据溴隐亭使用的方案不同分为两组,Ⅰ组48例,溴隐亭治疗初始剂量为5mg/d,使催乳素水平维持正常后逐渐减少溴隐亭用量(每天减少1.25 mg)至溴隐亭维持量为1.25～2.5 mg/d,至少3周.然后于月经第3～5天,加用枸橼酸氯米芬(CC)促排卵治疗,CC用药期间溴隐亭用量继续维持在1.25-2.5 mg/d,月经第9天B超检查若无优势卵泡生长则加用尿促性素(hMG)75U/d,直至卵泡直径达18mm时,改用人绒毛膜促性腺激素(hCG)6000～10000 IU,hCG用药后第2天及第3天指导同房或行人工授精;Ⅱ组15例,溴隐亭初始治疗剂量同Ⅰ组,并在开始溴隐亭治疗的同时进行促排卵药物治疗,用法也同Ⅰ组.分析两组促排卵用药剂量和治疗效果.结果 Ⅰ组与Ⅱ组在指导同房周期中比较,hMG用药天数平均减少5d,差异有统计学意义(P=0.004).Ⅰ组与Ⅱ组在人工授精周期中比较,hMG用药天数平均也减少5d,差异也有统计学意义(P=0.009).Ⅰ组妊娠率为40%(19/48)高于Ⅱ组的27%(4/15),但两组比较,差异无统计学意义(x2=0.403,P=0.525).结论 对于伴催乳素水平升高的PCOS不孕患者,先用溴隐亭治疗可以减少促排卵药物使用剂量及时间;溴隐亭和促排卵药物同时治疗可减少不孕症治疗的时间.     

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.