Effect of growth hormone administration on human ovarian function and steroidogenic gene expression in granulosa-luteal cells.

OBJECTIVE: To study the effect of growth hormone (GH) in combination with an ultrashort-term gonadotropin-releasing hormone analogue/human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) regimen in ovarian hyperstimulation for in vitro fertilization (IVF). DESIGN: Prospective randomized placebo-controlled study. SETTING: University-based IVF program. PATIENTS: Fifty-four normally cycling women (27 control and 27 GH-treated) participated in this study. INTERVENTIONS: Human recombinant GH (24 IU)/placebo was given intramuscularly on alternate days starting on cycle day 4 until the day of last hMG injection. RESULTS: Serum estradiol (E2) and progesterone (P) concentrations were slightly lower in the GH group than in the placebo group on the day of hCG injection and 1 day thereafter (P < 0.01 to 0.001). Serum luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone (T), and sex hormone-binding globulin did not differ between the groups. The follicular fluid (FF) concentration of T was higher in the GH group than in the placebo group (15.9 +/- 6.0 nmol/L versus 10.2 +/- 4.9 nmol/L, P < 0.005), and no differences were observed in the FF concentrations of E2, P, and insulin-like growth factor I between the groups. In granulosa cells isolated from patients who received GH treatment, the levels of 3 beta-hydroxysteroid dehydrogenase and aromatase messenger ribonucleic acid were significantly higher than in the patients receiving placebo. The number of hMG ampules needed for follicular development and the number of follicles and oocytes recovered were similar in both groups. CONCLUSIONS: These results indicate that GH administration modifies ovarian steroidogenic response to gonadotropins in IVF patients, suggesting a role for GH in the regulation of human ovarian function.     

Follicular fluid norepinephrine and dopamine concentrations are higher in polycystic ovary syndrome

The aim of the present study was to compare follicular fluid (FF) levels of norepinephrine (NE) and dopamine (DA) in polycystic ovary syndrome (PCOS) and non-PCOS patients who underwent in vitro fertilization (IVF). Forty-seven PCOS patients (study group) and 61 patients with male factor infertility (control group) who underwent IVF using GnRH agonist protocol were recruited. Concentrations of NE and DA were measured in FF specimens of all patients. Demographic characteristics were comparable between the groups. Significantly higher levels of NE were measured in FF of PCOS patients (median: 61.05?nmol/l) compared to those with male infertility (median: 49.82?nmol/l). Similarly, significantly higher levels of DA were measured in FF of PCOS patients (median: 23.70?nmol/l) compared to those with male infertility (median: 18.28?nmol/l). In conclusion, the FF concentrations of both catecholamine are increased in PCOS patients when compared to non-PCOS patients.     

Induction of preovulatory luteinizing hormone surge and prevention of ovarian hyperstimulation syndrome by gonadotropin-releasing hormone agonist

OBJECTIVE: To use gonadotropin-releasing hormone agonist (GnRH-a) instead of human chorionic gonadotropin (hCG) to induce oocyte maturation for in vitro fertilization (IVF). DESIGN: Pituitary and ovarian responses to GnRH-a and the outcome of IVF were studied prospectively. Data from patients injected with hCG were analyzed retrospectively. SETTING: Program of IVF at the Rambam (Governmental) Hospital, Haifa, Israel. PATIENTS AND INTERVENTIONS: One or two doses of buserelin acetate 250 to 500 micrograms were administered to six patients with moderate response (Estradiol [E2], 1,494 +/- 422 [+/- SD] pg/mL) and 8 patients with exaggerated response (E2, 7,673 +/- 3,028 pg/mL) to gonadotropin stimulation. Progesterone (P) and E2 were administered for luteal support. MAIN OUTCOME MEASURES: Gonadotropin-releasing hormone agonist effectively triggered luteinizing hormone (LH)/follicle-stimulating hormone (FSH) surge. Mature oocytes were recovered in all patients. Luteal E2 and P were lower than in patients injected with hCG. No signs of ovarian hyperstimulation syndrome were observed. RESULTS: Serum LH and FSH rose over 4 and 12 hours, respectively, and were significantly (P less than 0.05) elevated for 24 hours. Of all mature oocytes, 67% fertilized and 82% cleaved. Four pregnancies were obtained. CONCLUSIONS: A bolus of GnRH-a is able to trigger an adequate midcycle LH/FSH surge, resulting in oocyte maturation and pregnancy. Our preliminary results also suggest that it allows a more accurate control of ovarian steroid levels during the luteal phase and may prevent the clinical manifestation of ovarian hyperstimulation syndrome.     

The relative success of gonadotropin-releasing hormone analogue, clomiphene citrate, and gonadotropin in 1,099 cycles of in vitro fertilization.

OBJECTIVES: To evaluate the effectiveness of and analyze the factors influencing the outcome of three ovarian stimulation protocols used during in vitro fertilization (IVF) in a large population. DESIGN: Retrospective file review. SETTING: In vitro fertilization program in one center during the years 1985 to 1990. PATIENTS AND PROTOCOLS: Three hundred forty-one patients received clomiphene citrate (CC) and human menopausal gonadotropin (hMG), 365 received hMG alone, and 393 received gonadotropin-releasing hormone analogue (GnRH-a) for pituitary suppression followed by hMG stimulation. MAIN OUTCOME MEASURE: Rates of cancellation, total pregnancies, and ongoing pregnancies, with breakdown by age of patients. RESULTS: The cancellation rate because of early luteinization following GnRH-a/hMG was significantly reduced compared with the other two protocols: 3.6% versus 9.4% and 13.7% for CC/hMG and hMG, respectively. However, in women over 40 years of age, GnRH-a/hMG resulted in the highest rate of poor ovarian response. Significantly more oocytes were retrieved, fertilized, and cleaved after the use of GnRH-a/hMG compared with the other two protocols. Despite this, clinical pregnancy rate (PR) was the highest with CC/hMG compared with GnRH-a/hMG and hMG:31.4% versus 16.9% and 15.7%, respectively. Ongoing PRs were 20.5%, 9.7%, and 11.6%, respectively. CONCLUSIONS: Although the use of GnRH-a for pituitary suppression before ovarian stimulation for IVF reduced the cancellation rate and increased the number of retrieved oocytes, it was not found to result in higher PRs than those achieved by stimulation with CC/hMG. This suggests that treatment by GnRH-a/hMG should be reserved mainly for the prevention of early luteinization.     

The outcome of in vitro fertilization and embryo transfer in women with polycystic ovary syndrome failing to conceive after ovulation induction with exogenous gonadotropins.

OBJECTIVE: To assess the outcome of in vitro fertilization and embryo transfer (IVF-ET) in women with refractory polycystic ovarian syndrome (PCOS). DESIGN: Retrospective case series with an age-matched control group. SETTING: Ovulation induction and IVF programs in a tertiary referral center. PATIENTS AND INTERVENTIONS: Nine patients with PCOS who failed standard ovulation induction treatment (clomiphene citrate plus greater than or equal to 6 ovulatory human menopausal gonadotropin [hMG] cycles) underwent 19 cycles of IVF-ET. Forty age-matched tubal factor patients who completed 40 cycles of IVF-ET served as a control group. OUTCOME MEASURES: Demographic features and IVF-ET cycle characteristics were compared using Student's t-test and Fisher's exact test. RESULTS: Cycles of IVF-ET in patients with PCOS were associated with higher estradiol levels (5,222 versus 4,009 pmol/L), lower hMG requirements (15.8 versus 19.6 vials), greater numbers of oocytes (7.6 versus 5.6), and lower fertilization rates (56% versus 75%) compared with tubal factor cycles (P less than 0.05). However, the number of embryos transferred (3.9 versus 4.0) and the clinical pregnancy rate per embryo transfer (24% versus 25%) did not differ significantly between the two groups. CONCLUSION: These results suggest that conception failure after six or more ovulatory hMG cycles in patients with PCOS does not adversely affect subsequent IVF performance.     

肾素活性、血管紧张素Ⅱ与卵巢过度刺激综合征的相关性研究

目的探讨肾素活性(RA)及血管紧张素Ⅱ(AⅡ)与卵巢过度刺激综合征(OHSS)发病的相关性.方法用放射免疫(RIA)法测定32例超排卵治疗患者、10例OHSS患者与5例自然周期不孕症患者的血浆,21例超排卵患者、7例OHSS患者的卵泡液,3例OHSS患者胸、腹水,5例自然周期不孕患者腹腔液,6例卵巢癌患者腹水中的RA及AⅡ水平.结果血浆RA、AⅡ水平在自然周期与超排卵后卵巢不同反应状态下,均呈从晚卵泡期至围排卵期、中黄体期逐渐递增趋势,晚黄体期未妊娠时二者水平则下降,妊娠则大多上升;OHSS患者中黄体期血浆RA与AⅡ水平分别为(19.9±19.0) μg*L-1*h-1 与(397.0±378.2) ng/L,均显著高于其他患者(P<0.01～0.05);超排卵患者中黄体期与晚卵泡期二者水平比较,差异有显著性(P<0.05);用与未用白蛋白预防OHSS的患者间,各期血浆二者水平差异均无显著性(P>0.05);OHSS患者治疗后血浆中二者水平呈非常显著性的下降趋势.卵泡液中AⅡ水平、卵巢高反应者与OHSS患者卵泡液中的RA水平,均显著高于同期血浆.3例OHSS患者胸、腹水中RA、AⅡ水平,高于同期血浆水平,但不孕患者腹腔液与卵巢癌患者腹水中的水平极低.结论 RA、AⅡ与OHSS的病理生理过程密切相关,可能是其发病的重要原因之一.     

Insulin-like growth factor I (IGF-I) levels in follicular fluid from human preovulatory follicles: correlation with serum IGF-I levels

Insulin-like growth factor I (IGF-I) levels were measured in both serum and fluid of preovulatory follicles (n = 156) in 43 women undergoing in vitro fertilization (IVF). The mean IGF-I level in follicular fluid (FF) was significantly lower than in serum (0.52 +/- 0.02 IU/L versus 0.66 +/- 0.23 IU/L), and FF levels were significantly correlated with individual serum IGF-I levels as well as with follicular size and FF volume but not with oocyte maturity, granulosa cell appearance, or IVF. This suggests that FF IGF-I levels cannot serve as a clinical indicator for the degree of oocyte/granulosa cell differentiation or a predictor for IVF. Serum IGF-I levels were inversely correlated with the number of human menopausal gonadotropin ampules administered during treatment, suggesting that IGF-I might enhance ovarian gonadotropic stimulation.     

Progesterone levels on the day of human chorionic gonadotropin administration in cycles with gonadotropin-releasing hormone agonist suppression are not predictive of pregnancy outcome

In in vitro fertilization (IVF) cycles using gonadotropin-releasing hormone agonist (GnRH-a) suppression, we investigated whether an elevated progesterone (P) level on the day of human chorionic gonadotropin (hCG) administration indicates premature luteinization and is associated with a lower pregnancy rate. We retrospectively studied 101 patients treated with the GnRH-a leuprolide acetate, begun in the luteal phase of the prior menstrual cycle and continued until the day of hCG administration. On the day of hCG, 72 patients had P less than 0.9 ng/mL and 29 had less than or equal to 0.9 ng/mL. Patients in the high P group had a significantly greater estradiol level on the day of hCG. No significant difference in clinical pregnancy rates or ongoing pregnancy rates occurred between the low P and high P groups. We conclude that in IVF cycles pretreated with GnRH-a, P levels on the day of hCG are not predictive of conceiving in that cycle.     

Increased progesterone/estradiol ratio in the late follicular phase could be related to low ovarian reserve in in vitro fertilization-embryo transfer cycles with a long gonadotropin-releasing hormone agonist

OBJECTIVE: To gain insight into the physiologic as well as the clinical significance of premature luteinization in the long gonadotropin-releasing hormone agonist (GnRH-a) cycles and to evaluate whether it may be a manifestation of low ovarian reserve. DESIGN: Prospective evaluation. SETTING: A university-affiliated reproductive medicine unit. PATIENT(S): Seventy-six consecutive infertile women. INTERVENTION(S): The long GnRH-a protocol was used for IVF-ET treatment. MAIN OUTCOME MEASURE(S): Women in the study were prospectively evaluated in their first cycle of treatment and were divided into those with (study group) or without premature luteinization (control group). Premature luteinization was defined as P/E2 ratio of more than 1 on the day of hCG administration. RESULTS(S): Thirty-one (41%) of the women in the study demonstrated premature luteinization. Patients' characteristics were comparable between the two groups. Late follicular P/E2 ratio was significantly and considerably higher in the study as compared to the control group, 2.4 +/- 1.7 and 0.7 +/- 0.2, respectively. Ovarian reserve parameters including day 3 FSH, E2 level on hCG day, total amount of hMG, number of follicles, oocytes, and embryos were significantly inferior in the study as compared to the control group. P levels on hCG day were significantly higher in the study as compared to the control group, 1.9 +/- 0.7 ng/mL and 1.2 +/- 0.6 ng/mL, respectively. However, LH levels on hCG day did not differ between the groups, 1.4 +/- 0.7 mIU/mL and 1.2 +/- 0.7 mIU/mL, respectively. The clinical pregnancy rate was significantly lower in the premature luteinization group as opposed to controls, 13% and 42%, respectively. CONCLUSION(S): Premature luteinization, defined as late follicular P/E2 >1, in long GnRH-a cycles seems to adversely affect clinical outcome. Our findings in this setting support the notion that premature luteinization could be related to low ovarian reserve and that this manifestation is not necessarily an LH-dependent event.     

促性腺激素释放激素激动剂长、短方案在体外受精-胚胎移植中的比较性研究

目的　探讨促性腺激素释放激素激动剂（GnRH-a）长、短方案控制性超排卵在体外受精-胚胎移植（IVF-ET）中的疗效。方法　将2000年1～5月进行IVF和单精子卵胞浆注射（ICSI）助孕的不孕患者，按病历奇、偶数编号分为GnRH-a长方案组（55例）和短方案组（54例）。长方案组从使用促性腺激素（Gn）治疗周期前的黄体中期开始使用GnRH-a0.9mg/d，至垂体完全降调节后，加用Gn；短方案组从月经第2天开始使用GnRH-a0.45mg/d，同时加用Gn。两组均在优势卵泡达18mm时，肌内注射人绒毛膜促性腺激素（hCG），36h后取卵行IVF及ICSI。结果　长方案组较短方案组，使用Gn前血清促卵泡激素（FSH）和黄体生成素（LH）水平降低［（4.4±1.2）IU/L比（6.3±1.7）IU/L,（2.7±1.5）IU/L比（4.4±2.8）IU/L,P<0.01］；注射hCG前血清雌二醇（E2）和LH水平降低［（7119±3584）pmol/L比（9523±3587）pmol/L，（1.0±1.0）IU/L比（4.0±3.4）IU/L,P<0.01］；每个卵子E2水平降低［（610±315）pmol/L比（935±450）pmol/L,P<0.01］；Gn用量增多［（28.0±8.6）支比（23.4±8.7）支,P<0.01］，用药时间增长［（11.1±1.2）d比（10.1±1.5）d,P<0.01］；两组平均获卵数、第2次成熟分裂中期卵子数、受精卵数、卵裂数、优质胚胎数及妊娠率无显著差异。结论　在IVF-ET，GnRH-a长、短方案能获得相同的控制性超排卵效果，且GnRH-a短方案能减少Gn用量和缩短治疗时间。     

Outcome of ovarian response after suppression with a gonadotropin releasing hormone agonist in different chronological periods prior to gonadotropin stimulation for in vitro fertilization.

Gonadotropin-releasing hormone analogues (GnRH-a) are currently used in combination with gonadotropins in ovarian stimulation for in vitro fertilization programs (IVF). The present study aims at evaluating the treatment cycles for IVF for which human menopausal gonadotropin (HMG) was initiated only when pituitary desensitization was confirmed regardless of the time of GnRH-a administration. Two groups of patients were examined. Patients in group A (n = 46) were commenced with HMG treatment on day 15 when E2 level was less than 40 pg/ml. Group B patients (n = 27) comprised the cycle treatments in which E2 levels were greater than 40 pg/ml on day 15. In these cases HMG was first given when E2 levels declined to less than 40 pg/ml. The fertilization rate was similar in both A and B groups, 71.6 and 67.7% respectively. The pregnancy rate per transfer was 27.5 and 34.6% in group A and B respectively. Multiple pregnancies were found at 18.1% in group A versus 44.4% in group B. It is concluded that postponement of HMG administration in patients with high levels of E2 on day 15 after GnRH-a administration seems to offer an improvement in embryo cleavage speed, pregnancy rate and multiple pregnancies.     

Elevated ovarian pentraxin 3 in polycystic ovary syndrome

PurposePentraxin 3 (PTX3) plays a crucial role in cumulus expansion and fertilization. The ovarian PTX3 level in polycystic ovary syndrome (PCOS) remains uncertain. In the present study, we investigated the follicular PTX3 levels and found the influence of reproductive hormones on ovarian PTX3 concentration.MethodsThis study was based on 204 healthy-weight women (102 PCOS and 102 normal ovulating subjects) undergoing in vitro fertilization (IVF). Follicular fluid (FF) was collected during oocyte retrieval. The PTX3 levels and other hormone levels in FF samples were analyzed by enzyme-linked immunosorbent assay (ELISA).ResultsThe PTX3 level in the follicle was significantly higher in the healthy-weight PCOS women than controls. Positive correlations were found between ovarian PTX3 level and the existence of PCOS, cycle length, basal LH to FSH ratio and TT in serum, antral follicle count, and ovarian insulin and androgen level, and inverse correlations with the basal serum PRL and ovarian SHBG. In multivariant linear regression analysis, the presence of PCOS diagnosis, participants’ basal LH to FSH ratio, and ovarian androstenedione level were the main predictors of ovarian PTX3 level among the enrolled subjects.ConclusionElevated ovarian PTX3 level supports the low-grade chronic inflammatory state in the follicles of PCOS. The existence of PCOS, disturbed pituitary gland, and ovarian hyperandrogenism might also be related to this state of low-grade chronic inflammation and could be a subject of further study.     

The gonadotropin-releasing hormone agonist stimulation test--a sensitive predictor of performance in the flare-up in vitro fertilization cycle

OBJECTIVE: To evaluate the initial versus early pattern of estradiol (E2) change after administration of a gonadotropin-releasing hormone agonist (GnRH-a), i.e., the GnRH-a stimulation test versus E2 pattern, respectively, as predictors of ovarian response and pregnancy in in vitro fertilization (IVF) patients stimulated with a flare-up protocol. DESIGN: Prospective study in a consecutive group of patients. SETTING: Tertiary care, institutional setting. PATIENTS: Two hundred twenty-eight patients entered and completed the study. The only patients excluded from study were those anticipated to have polycystic ovarian disease, those with a single ovary, or those with an ovarian cyst(s). INTERVENTIONS: Patients were stimulated with a GnRH-a flare-up protocol beginning on menstrual day 2. MAIN OUTCOME: Evaluation of the GnRH-a stimulation test and the E2 pattern as predictors of the number of mature oocytes retrieved and pregnancy. RESULTS: The GnRH-a stimulation test but not the E2 pattern was predictive of the number of mature oocytes retrieved (r = 0.53, P less than 1 X 10(-5) and pregnancy (chi 2 = 8.5, P = 0.04). The E2 pattern was predictive of the duration and number of ampules of gonadotropin required for stimulation. CONCLUSION: The GnRH-a stimulation test is a sensitive predictor of performance in the flare-up IVF cycle.     

Does transient hyperprolactinemia during ovarian hyperstimulation interfere with conception or pregnancy outcome?

The significance of transiently increased serum prolactin (PRL) levels on pregnancy rates in in vitro fertilization (IVF) is unknown. The aim of this study was to evaluate PRL levels in IVF patients who conceived and in matched controls who did not. Thirty-seven IVF cycles resulting in pregnancy and 74 nonpregnant cycles were compared. Prolactin was measured before ovarian stimulation with clomiphene citrate, and human menopausal gonadotropin and estradiol (E2) and PRL were measured 8 hours after human chorionic gonadotropin (hCG) administration at midcycle. Before ovarian stimulation, serum PRL levels were not different in the pregnant and nonpregnant women (11.1 +/- 0.6 [mean +/- standard error] micrograms/l and 10.1 +/- 0.4 micrograms/l, respectively). After hCG, PRL levels were significantly higher in the pregnant women than in the nonpregnant women (20.8 +/- 1.6 and 16.0 +/- 0.9 micrograms/l, respectively; P less than 0.005) and more pregnant than nonpregnant women had elevated PRL levels (49% versus 28%, respectively; P less than 0.05). There was no correlation between PRL and E2 in either group. The abortion rate was not different between the women with elevated PRL (22.2%) and the normoprolactinemic women (31.6%). These results do not support treatment of transient hyperprolactinemia with dopamine agonists in IVF patients.     

Impact of metformin therapy on ovarian stimulation and outcome in 'coasted' patients with polycystic ovary syndrome undergoing in-vitro fertilization

This study was designed to determine if metformin therapy improves ovarian stimulation and IVF outcomes in coasted patients with clomiphene-resistant polycystic ovarian syndrome (PCOS). A retrospective data analysis was performed on women with clomiphene citrate-resistant PCOS treated with or without metformin, who underwent 72 cycles of IVF-embryo transfer with intracytoplasmic sperm injection (ICSI). In 59 cycles, patients were coasted to allow oestradiol concentrations to drop before human chorionic gonadotrophin administration. In patients undergoing coasting, the outcome of IVF with ICSI was compared in those who were treated and untreated. In patients treated with metformin, follicular fluid concentrations of testosterone and insulin were significantly lower (60.5 +/- 5 versus 79.1 +/- 6 ng/dl; P < 0.05 and 18 +/- 2.5 versus 22 +/- 2.4 micro IU/ml; P < 0.05 respectively), and the mean number of oocytes retrieved (22.3 +/- 2.4 versus 19.7 +/- 1.6) did not differ. The metformin-treated group showed an increase in the mean number of mature oocytes, oocytes fertilized and cleaving embryos (4-cell or greater by 72 h). However, in the group of patients undergoing coasting, maximum oestradiol concentrations and number of days of coasting were all lower in the metformin-treated group with increased clinical pregnancy rates (71 versus 30%, P < 0.05). Therefore, metformin use appears beneficial in improving IVF outcomes in clomiphene citrate-resistant PCOS patients.     

Interest of growth hormone-releasing hormone administration for improvement of ovarian responsiveness to gonadotropins in poor responder women.

OBJECTIVE: We have investigated the beneficial effect of a somatotroph axis stimulation on ovarian response to gonadotropin. DESIGN: Growth hormone-releasing hormone (GH-RH) was administered in a prospective study in women undergoing an in vitro fertilization protocol. PATIENTS: Twelve patients were selected for their poor ovarian response to previous stimulations using gonadotropin-releasing hormone analog (GnRH-a) and human menopausal gonadotropins (hMG). INTERVENTIONS: Five hundred micrograms of GH-RH1-29 were administered two times daily concomitantly with GnRH-a and hMG from day 2 of the cycle to the time of ovulation. MAIN OUTCOME MEASURES: Stimulation of somatotroph axis was appreciated by measuring over-night urinary growth hormone (GH) output, plasma GH, and insulin-like growth factor I (IGF-I) and follicular fluid (FF) IGF-I. The effects of GH-RH administration on ovarian function were determined by plasma estradiol levels and follicular data. RESULTS: Administration of GH-RH was associated with a significant improvement of urinary (P less than 0.025) and plasma (P less than 0.001) GH concentrations and of the hormonal response to hMG (P less than 0.01). Levels of IGF-I followed a biphasic plasma variation, and a slight increase in recruited follicles, retrieved oocytes, and FF IGF-I content was also observed. CONCLUSIONS: Activation of the somatotroph axis by GH-RH enhances the hormonal ovarian response to hMG and may be an adjunctive therapy to improve follicular maturation.     

Anti-annexin V antibodies in patients with early pregnancy loss or implantation failures

OBJECTIVE: To examine the impact of flare (short) vs. down-regulation (long) GnRH agonist (GnRH-a) on serum and follicular fluid (FF) LH and androgen concentrations in women undergoing IVF treatment cycles. DESIGN: Prospective observational study. SETTING: IVF clinic. PATIENT(S): One hundred sixteen ovulatory subjects undergoing IVF. INTERVENTION(S): Fifty-eight ovulatory patients undergoing a down-regulation regimen matched with 58 undergoing the flare regimen as part of an IVF cycle. MAIN OUTCOME MEASURE(S): Serum concentrations of LH, FSH, Progesterone (P4), Androstenedione (A), T, and E(2) on the day of hCG administration were compared between the two groups. In addition, the FF P4, 17OHP4, A, T, and E(2) levels were compared in the two groups. RESULT(S): Serum LH was significantly higher with the flare regimen (15.2 +/- 1.14 IU/L, P<.05) when compared with results with the down-regulation protocol (9.5 +/- 0.77 IU/L). In addition, FF A was significantly higher in the flare protocol (57.3 +/- 13.3 ng/mL, P<.05) compared with in the down-regulation protocol (27 +/- 2.44 ng/mL). Serum and FF P4, 17OH P4, T, and E(2) were not statistically significantly different between the two groups. CONCLUSION(S): Serum LH and FF A are significantly higher in the flare regimen in comparison with the down-regulation regimen. Circulating LH appears to play a role in determining FF A concentration.     

Transvaginal ovarian drilling: a new surgical treatment for improving the clinical outcome of assisted reproductive technologies in patients with polycystic ovary syndrome

OBJECTIVE: To evaluate the efficacy of transvaginal ovarian drilling (TVOD) in patients with polycystic ovary syndrome (PCOS) who were undergoing IVF treatment. DESIGN: Pilot study. SETTING: Reproductive medicine unit. PATIENT(S): Eleven patients with PCOS undergoing treatment with assisted reproductive technology (ART). INTERVENTION(S): Selection criterion for TVOD was repeated poor performance in > or =2 previous IVF cycles. MAIN OUTCOME MEASURE(S): Controlled ovarian hyperstimulation parameters, number of eggs collected, fertilization rate, embryo cleavage rate, implantation rate, pregnancy rate compared with the cycles before TVOD. RESULT(S): In the cycle after TVOD, a significantly higher dosage of FSH was used (33.5 +/- 12 IU vs. 52.2 +/- 15 IU) to collect a higher number of oocytes in the presence of similar E2 values at the day of hCG administration. This resulted in significantly higher fertilization and cleavage rates (27% vs. 66% and 54% vs. 72%, respectively). The pregnancy and the implantation rates after TVOD were similar to those for normovulatory patients undergoing IVF for tubal factor infertility during the study period. CONCLUSION(S): Our data suggest that the TVOD is effective in improving IVF results in difficult to treat patients with PCOS, and it is less invasive and less expensive when compared with laparoscopic ovarian diathermy.     

血清抑制素水平在体外受精-胚胎移植超排卵周期中预测卵巢反应性的价值

目的探讨血清抑制素水平在体外受精-胚胎移植(IVF-ET)超排卵周期中与卵巢反应性的相关性及其预测价值。方法对37例初次接受IVF-ET、基础卵泡刺激素(FSH)水平<12U/L的患者,于IVF前1周期月经第2~4天及黄体中期、IVF周期重组rFSH注射第5天、人绒毛膜促性腺激素(hCG)注射日、取卵日及黄体中期,分别检测血清雌二醇、孕酮、抑制素(INH)A及INHB水平。根据IVF周期中的获卵数、雌二醇峰值水平、是否发生卵巢过度刺激综合征(OHSS)的情况,将37例患者分为卵巢低反应者8例(A组)、卵巢正常反应者及卵巢高反应者29例(B组),比较两组IVF-ET临床效果及注射rFSH前后INH、雌二醇及孕酮水平的变化。通过多重逻辑回归分析、受试者工作特征曲线分析,评价各激素水平预测卵巢反应性的准确性;通过敏感度、特异度的计算确定INHB诊断的临界值。结果(1)A、B组IVF前1周期月经第2~4天INHB水平分别为(37±35)、(91±90)ng/L;IVF周期注射rFSH第5天的INHB水平分别为(194±157)、(2254±4765)ng/L,INHA水平分别为(36±35)、(91±90)ng/L,两组比较,差异有统计学意义(P<0·05)。(2)获卵数与IVF前1周期月经第2~4天INHB水平、IVF周期rFSH注射后各阶段的INHB、INHA及雌二醇水平呈显著正相关(INHB:r=0·39~0·67,P<0·05;INHA:r=0·43~0·59,P<0·01;雌二醇:r=0·50~0·60,P<0·01)。(3)受试者工作特征曲线分析显示,注射rFSH第5天的INHB水平的最大的曲线下面积为0·948(95%可信限为0·871~1·025),将INHB为400ng/L作为临界值时,其对卵巢反应性的预测敏感度为82·8%,特异度为99·1%。结论基础INHB水平、IVF周期rFSH注射第5天的INHB水平均是预测卵巢反应性较好的标记物;IVF周期rFSH注射第5天的INHB水平对卵巢反应性具有最佳的预测价值。     

A prospective randomized comparison of luteal phase versus concurrent follicular phase initiation of gonadotropin-releasing hormone agonist for in vitro fertilization.

OBJECTIVE: To compare the effects of gonadotropin-releasing hormone agonist (GnRH-a) initiation either preceding or concurrent with controlled ovarian hyperstimulation (COH) in patients undergoing in vitro fertilization-embryo transfer (IVF-ET). DESIGN: Fifty-five patients were prospectively randomized to receive either GnRH-a on cycle day 21 before COH until ovarian suppression was achieved (group I) or GnRH-a concurrently with COH commencing on cycle day 3 (group II). MAIN OUTCOME MEASURES: Serum gonadotropin and ovarian steroid hormone levels, as well as fertilization, spontaneous abortion, and live birth rates. RESULTS: Twenty-six patients in group I and 29 patients in group II underwent COH for IVF-ET. Patients in group II had significantly higher serum luteinizing hormone, progesterone, and testosterone levels during stimulation with human menopausal gonadotropins (hMG) before oocyte retrieval (P < 0.05). Despite similar fertilization, biochemical, and clinical pregnancy rates, the spontaneous abortion rate was higher in group II (5/6) compared with group I (1/7) (P < 0.05). Thus, the live birth rate/retrieval for group I was 6 of 24 (25%) as compared with that of group II, which was 1 of 26 (3.8%) (P < 0.05). CONCLUSIONS: The initiation of GnRH-a in the follicular phase concurrently with hMG is associated with evidence of premature luteinization, hyperandrogenemia, and poorer pregnancy outcome compared with luteal phase administration of GnRH-a before hMG for IVF-ET.