The effect of growth hormone supplementation on in vitro fertilization outcome: a prospective randomized placebo-controlled double-blind study.

OBJECTIVE: To determine the effect of growth hormone (GH) supplementation to a long gonadotropin-releasing hormone agonist (GnRH-a)/human menopausal gonadotropin (hMG) treatment protocol, on ovarian response, embryo quality, and clinical outcome in in vitro fertilization (IVF). DESIGN: Growth hormone or placebo were administered in a prospective randomized double-blind manner. PATIENTS: Forty-two normal ovulatory, women who were 38 years of age or less with mechanical factor infertility and a normal male factor were selected for this study. INTERVENTIONS: Gonadotropin-releasing hormone agonist, 0.5 mg/d, was initiated in the midluteal phase of the preceding cycle and continued until the day of human chorionic gonadotropin (hCG) administration. Ovulation induction with hMG was started 14 days after pituitary down regulation (17 beta-estradiol [E2] serum level less than 30 pg/mL). Growth hormone (12 IU/d) or placebo were administered on days 1, 3, 5, and 7 of hMG treatment. RESULTS: Breaking the code at the completion of the study revealed that 20 women received GH and 22 placebo. The age and duration of infertility did not differ between the two groups. Follicular phase duration, hMG ampules used, serum E2, and number of follicles (greater than or equal to 14 mm) on day of hCG as well as number of oocytes and embryos achieved were similar in both groups. Embryo morphology and rate of cleavage were also similar. Insulin-like growth factor-I (IGF-I) serum levels did not change after pituitary down regulation and increased significantly both after GH/hMG and placebo/hMG ovulation induction treatment. Clinical pregnancy rate (PR) per embryo transfer and implantation rate were 40% versus 32% and 17.9% versus 11.3% in the GH and placebo groups, respectively, and were not statistically different. CONCLUSIONS: In normo-ovulatory women undergoing ovulation induction for IVF, GH supplementation to hMG after GnRH-a pituitary down regulation does not seem to augment ovarian response or improve embryo quality. The effect of this regimen on actual PRs and implantation rates needs further clarification.     

Altered follicular development in clomiphene citrate versus human menopausal gonadotropin-stimulated cycles for in vitro fertilization

The pattern of periovulatory and luteal phase serum estradiol (E2) and progesterone (P) as well as follicular fluid (FF) E2, P, androgen, gonadotropin, and prolactin concentrations of eight women undergoing clomiphene citrate (CC)/human chorionic gonadotropin (hCG) stimulation and eight women undergoing human menopausal gonadotropin (hMG)/hCG stimulation of follicular development for the purpose of in vitro fertilization were compared. Ovulation was induced with either a 5-day course of CC (100 mg/day beginning on day 5 of the cycle) or an individualized hMG regimen, and laparoscopy was performed 36 hours after hCG administration. The length of the luteal phase was significantly longer (P less than 0.05) in the CC-treated group as compared with the hMG-treated group. The pattern of serum E2 levels differed significantly (P less than 0.01) in that E2 levels were lower in the early and midluteal phase in CC-stimulated cycles; in addition, a delayed second E2 peak was observed in the late luteal phase in these women. Serum P levels, however, were lower in the hMG-stimulated group. Analysis of FF hormone concentrations revealed significantly (P less than 0.05) higher concentrations of E2 and androsterone in the FF of hMG-treated patients. It is concluded that follicular development in CC-stimulated cycles differs markedly from that in hMG-stimulated cycles. These differences may reflect either an altered follicular maturational process or may represent a direct inhibitory effect of CC on follicular steroidogenesis.     

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.     

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.     

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.     

Lack of insulin-like growth factor binding protein-3 variation after follicle-stimulating hormone stimulation in women with polycystic ovary syndrome undergoing in vitro fertilization.

OBJECTIVE: To investigate serum and follicular fluid (FF) insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) behavior in superstimulated cycles in patients with polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: Department of Obstetrics and Gynecology, University of Naples. PATIENT(S): Thirty-two patients with regular menses and tubal and/or male factor infertility and 21 patients with PCOS undergoing IVF. INTERVENTION(S): The IVF program used leuprolide acetate suppression followed by sequential hMG in the subsequent cycle. After follicular development, hCG administration was followed 34-36 hours later by oocyte retrieval. MAIN OUTCOME MEASURE(S): E2, GH, IGF-I, and IGFBP-3 assayed by RIA and immunoradiometric assay. RESULT(S): The controls and patients with PCOS showed similar increases in E2 and GH titers in response to FSH stimulation. Serum IGF-I did not change in either group and was equivalent in the FF. Patients with PCOS had a higher FF IGFBP-3 titer and did not show the decrease in serum IGFBP-3 levels of the control group after FSH stimulation. CONCLUSION(S): The apparent failure of IGFBP-3 reduction in patients with PCOS alters IGF-I bioavailability. Increased sequestration of IGF-I affects ovarian steroidogenesis and may explain the poor response to gonadotropin stimulation.     

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。     

Manipulating the follicular phase in IVF cycles: a comparison of two hMG stimulation protocols

The results of two human menopausal gonadotropin (hMG) protocols of ovulation induction for in vitro fertilization (IVF) were compared. With the first protocol, 28 women (group 1) were treated with an hMG dosage which was increased stepwise. With the second, 30 women (group 2) were treated with a high dose of hMG for 2 days, then given a constant daily dose. The two groups were compared with regard to ovarian response, luteal phase and laboratory and clinical outcomes of IVF. They were comparable as regards the total number of hMG doses required, the number of large follicles (mean diameter greater than 15 mm) on day 0 (day of human chorionic gonadotropin (hCG) administration), serum estrogen (E2) and progesterone (P) levels throughout the cycle and IVF laboratory and clinical outcomes. They differed significantly (p less than 0.01) only in the number of secondary smaller follicles (mean diameter less than 15 mm) observed on day 0 (3.7 +/- 0.4 for group 1 and 5.3 +/- 0.4 for group 2). Manipulating the hMG dosage during the early-mid follicular phase does not affect follicular synchrony, the number of oocytes harvested and the number of embryos achieved.     

Pharmacokinetics of exogenous gonadotropin and ovarian response in in vitro fertilization.

OBJECTIVE: To assess the diffusion of gonadotropin into the follicular fluid (FF) and its relation to the results achieved in a human IVF-ET program. DESIGN: Retrospective pharmacokinetic study. SETTING: Fukuoka University Hospital, Japan. PATIENT(S): Eighty-seven infertile patients underwent 137 cycles of IVF-ET. INTERVENTION(S): Serum and FF were collected at the time of oocyte recovery. The hCG ratio (between follicular hCG and serum hCG concentrations, measured by time-resolved fluoroimmunoassay) was evaluated as an index of the diffusion of exogenous gonadotropin. MAIN OUTCOME MEASURE(S): Relation between hCG ratio and the results and outcome of the IVF-ET program. RESULT(S): The hCG ratio decreased with the total dosage of hMG and increased with the serum E2 level, the number of oocytes recovered, and the number of oocytes fertilized. Patients with a poor response showed a low hCG ratio, which was associated with a complete lack of fertilization. The mean hCG ratio in the pregnant cycles was significantly higher than that in the nonpregnant cycles. An hCG ratio > 0.46 was seen in all pregnant cycles. CONCLUSION(S): The diffusion of exogenous gonadotropin into the FF may be an important predictor of IVF outcome.     

An increased initial follicle-stimulating hormone/luteinizing hormone ratio does not affect ovarian responses and the outcomes of in vitro fertilization

The tenet that a combination of human follicle-stimulating hormone (hFSH)/human menopausal gonadotropin (hMG) improves follicular recruitment was assessed by randomly treating ovulatory women either with hFSH/hMG on days 3 and 4 of the cycle followed by two ampules of hMG daily or with a constant daily dose of 2 ampules of hMG. Estradiol (E2) levels on the day of human chorionic gonadotropin (hCG) and the mean number of mature, immature and atretic oocytes per cycle did not differ between the two groups. Likewise, fertilization, cleavage, and pregnancy rates were similar for the two treatments. When daily hormone levels were compared in 11 patients during two successive treatment cycles with both stimulation protocols, the temporal pattern of FSH accumulation was repeated in both cycles, but FSH levels were significantly higher when patients received hFSH/hMG. Nevertheless, during both cycles, E2 reached similar peak levels and the mean number of follicles per cycle on the day of hCG administration was not different. We conclude that routine use of hFSH/hMG does not improve the success of an in vitro fertilization (IVF) program and that higher FSH levels do not change the individuality of ovarian response in the same woman.     

Value of suppression with a gonadotropin-releasing hormone agonist prior to gonadotropin stimulation for in vitro fertilization

This study examined the use of gonadotropin-releasing hormone agonist (GnRHa) suppression before gonadotropin stimulation in 26 patients with failed prior in vitro fertilization (IVF) attempts and variable basal serum gonadotropin levels. Leuprolide, 1 mg subcutaneously per day, was administered from the midluteal phase of the cycle before IVF treatment. Concomitantly, stimulation was initiated on cycle day 3 with human menopausal gonadotropin (hMG) and follicle stimulating hormone (FSH). Based on their prior IVF attempts and serum gonadotropin levels on cycle day 3, 9 patients were high responders with elevated mean basal luteinizing hormone (LH)/FSH, 8 were low responders with elevated mean basal FSH/LH, 7 were intermediate responders with normal mean basal FSH/LH and a history of premature LH surge, and 2 had elevated (perimenopausal) mean FSH and LH. Leuprolide was discontinued on the day of human chorionic gonadotropin (hCG) administration. Prior IVF attempts in the same patients with the same protocol, but without GnRHa suppression, were used as controls. The mean number of ampules of hMG and FSH was significantly higher in leuprolide cycles than in controls. The mean day of hCG administration was also higher for leuprolide cycles than for controls. The mean LH and progesterone levels on the day of hCG were significantly lower in leuprolide cycles. The mean number of preovulatory oocytes aspirated and transferred was higher in leuprolide cycles. Cancellation and pregnancy rates were improved in leuprolide cycles. It is concluded that prior GnRHa suppression is beneficial for follicular recruitment for IVF. More patients with variable basal serum gonadotropin levels need to be studied before definite recommendations are made.     

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.     

Subtle progesterone rise in the single-dose gonadotropin-releasing hormone antagonist (cetrorelix) stimulation protocol in patients undergoing in vitro fertilization or intracytoplasmic sperm injection cycles.

A subtle rise in serum progesterone during the late follicular phase in patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles is a frequent event that can decrease implantation and pregnancy rates in controlled ovarian hyperstimulation (COH) protocols that use a gonadotropin-releasing hormone (GnRH) antagonist. The aim of the present study was to evaluate the prevalence and effect of the subtle progesterone rise during COH with single-dose GnRH antagonist in combination with clomiphene citrate (CC) and human menopausal gonadotropins (hMG) in IVF or ICSI cycles. Ninety-five women undergoing COH with CC, hMG and a single 2.5 mg dose of the GnRH antagonist, cetrorelix, were enrolled in the study. Patients were grouped according to serum progesterone level on the day of human chorionic gonadotropin (hCG) administration (P < 1.2 ng/ml or P >/= 1.2 ng/ml). The incidence of a subtle progesterone rise was 54.7% (52/95). The group with P >/= 1.2 ng/ml had significantly higher serum levels of luteinizing hormone (p = 0.002) and estradiol (p < 0.001) on the day of hCG injection than the group with P < 1.2 ng/ml, and more oocytes were retrieved (p = 0.001). However, there was no significant difference in fertilization, clinical pregnancy or implantation rate between the two groups. In conclusion, a subtle progesterone rise during the late follicular phase is common but not associated with pregnancy outcome.     

Controlled ovarian stimulation with exclusive FSH followed by stimulation with hCG alone, FSH alone or hMG

OBJECTIVE: To assess if low-dose hCG is similar to hMG and to rFSH in the late follicular phase. STUDY DESIGN: In a prospective randomized controlled trial, 51 patients undergoing controlled ovarian stimulation received ovarian priming with rFSH and then received hCG (200 IU/day) (hCG group, n=17), hMG (225 IU/day) (hMG group, n=17) or rFSH (200 IU/day) (FSH group, n=17) in the late stage of follicular development. Parameters of follicular response and serum estradiol, progesterone and testosterone levels were assessed. RESULTS: Pre-ovulatory ovarian follicle occurrence and length of treatment were similar among the three treatment groups. Serum progesterone level on the day of pre-ovulatory hCG was significantly higher in the hCG group than in the hMG or rFSH group. Clinical pregnancy rates were similar for all groups. The total cost of treatment was significantly lower for the hCG group than for the groups supplemented with hMG or rFSH. CONCLUSIONS: LH in the form of low-dose hCG during the late follicular phase induced the same follicular pattern as hMG and rFSH after ovulation induction. The procedure using hCG produced pregnancy rates similar to those obtained using hMG and rFSH, even though the patients showed higher serum progesterone levels on the hCG day.     

Cumulative ovulation rate in human menopausal/human chorionic gonadotropin-treated monkeys: "step-up" versus "step-down" dose regimens

Cumulative ovulation rates in monkeys given human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG) on menstrual cycle days 3 to 9 in a "step-up" versus "step-down" protocol were compared with those achieved by hMG only. Using direct ovarian observation to detect sites of follicular rupture, retrograde tubal irrigation to collect eggs or embryos, and serum estradiol and progesterone levels to infer changes in ovarian status, we counted the number of ovulations at intervals of 24, 48, 72, 96, and 120 hours after hCG or comparable intervals without hCG. The data indicate (1) whereas most ovulations occurred on or before day 3 after hCG treatment, when the "step-up" dose regimen was employed additional follicles had ruptured on days 4 and 5; (2) a "step-down" protocol for hMG therapy may better synchronize follicular rupture and reduce susceptibility to delayed ovulations compared with a "step-up" dose regimen; and (3) under hMG stimulation, few follicles would rupture spontaneously (without hCG or luteinizing hormone treatment).     

The effect of the day of initiation of ovarian stimulation in the day of luteinizing hormone surge and outcome of in vitro fertilization

It was hypothesized that the day of initiation of ovarian stimulation may influence the day of the luteinizing hormone (LH) surge onset and follicular development. Two groups of 52 patients were randomly selected to commence ovarian stimulation on either day 2 or day 4. The mean +/- standard deviation day of the LH surge was 11.0 +/- 0.9 for day 2 and 12.2 +/- 0.9 for day 4 (P less than 0.001), and the day of human chorionic gonadotropin (hCG) administration was 10.7 +/- 1.2 for day 2 and 11.4 +/- 0.9 for day 4 (P less than 0.02). The two groups also differed significantly in the mean number of days of human menopausal gonadotropin (hMG) administration (day 2, 7.4 +/- 2.7, versus day 4, 6.3 +/- 2.5), and the mean number of vials of hMG administered (day 2, 10.4 +/- 3.2, versus day 4, 8.1 +/- 2.9). However, the mean estradiol level on the day of the LH surge or hCG administration, the number of oocytes collected and fertilized, the number of embryos transferred, and the pregnancy rates were not significantly different. In conclusion, the day of the LH surge or hCG administration can be influenced by the day of initiation of ovarian stimulation, and the initiation of ovarian stimulation around day 4 of the menstrual cycle is clinically more efficient than initiation of follicular development early in the follicular phase.     

Intrafollicular and serum levels of leptin during in vitro fertilization cycles: comparison between the effects of recombinant follicle-stimulating hormones and human menopausal gonadotrophin

Objectives.?To compare the effect of recombinant follicle-stimulating hormones (r-FSH) and human menopausal gonadotrophin (hMG) on leptin levels in serum and follicular fluid (FF) during in vitro fertilization IVF/ET treatment, and to investigate whether leptin levels in the follicular fluid and/or serum are correlated with IVF success.

Methods.?Sixty-three patients undergoing IVF cycle were subdivided into two groups. r-FSH was used to for controlled ovarian hyperstimulation in 29 patients (Group A) while, hMG was used in 34 patients (Group B). Our main outcomes were serum and FF leptin on the day of oocyte collection.

Result(s).?The two groups were comparable in age, body mass index (BMI), indications for IVF/ET, E2 level on human chorionic gonadotrophin day, number of retrieved oocytes, fertilization rate, number of transferred embryos and pregnancy rate. Serum and FF leptin levels were similar between the two study groups. Additionally, no correlation was found between levels of leptin in either serum or FF and cycle results such as: number of retrieved oocytes, fertilization rate and pregnancy rate.

Conclusions.?r-FSH and hMG have been found to have comparable effects on leptin levels in the serum and the FF of patients undergoing IVF/ET. Additionally, leptin levels in both serum and FF on day of retrieval have no correlation to IVF/ET outcome.     

Subtle progesterone rise in the single-dose gonadotropin-releasing hormone antagonist (cetrorelix) stimulation protocol in patients undergoing in vitro fertilization or intracytoplasmic sperm injection cycles

A subtle rise in serum progesterone during the late follicular phase in patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles is a frequent event that can decrease implantation and pregnancy rates in controlled ovarian hyperstimulation (COH) protocols that use a gonadotropin-releasing hormone (GnRH) antagonist. The aim of the present study was to evaluate the prevalence and effect of the subtle progesterone rise during COH with single-dose GnRH antagonist in combination with clomiphene citrate (CC) and human menopausal gonadotropins (hMG) in IVF or ICSI cycles. Ninety-five women undergoing COH with CC, hMG and a single 2.5 mg dose of the GnRH antagonist, cetrorelix, were enrolled in the study. Patients were grouped according to serum progesterone level on the day of human chorionic gonadotropin (hCG) administration (P < 1.2 ng/ml or P ≥ 1.2 ng/ml). The incidence of a subtle progesterone rise was 54.7% (52/95). The group with P ≥ 1.2 ng/ml had significantly higher serum levels of luteinizing hormone (p = 0.002) and estradiol (p < 0.001) on the day of hCG injection than the group with P < 1.2 ng/ml, and more oocytes were retrieved (p = 0.001). However, there was no significant difference in fertilization, clinical pregnancy or implantation rate between the two groups. In conclusion, a subtle progesterone rise during the late follicular phase is common but not associated with pregnancy outcome.     

Cotreatment with growth hormone, after pituitary suppression, for ovarian stimulation in in vitro fertilization: a randomized, double-blind, placebo-control trial.

OBJECTIVE: To explore the effect of cotreatment with growth hormone (GH) for ovarian stimulation after pituitary suppression. DESIGN: A randomized, double-blind, placebo-controlled study. SETTING: Specialist Reproductive Endocrine and In Vitro Fertilization (IVF) Unit. PATIENTS, PARTICIPANTS: Twenty-five IVF patients who had responded suboptimally in a previous treatment cycle. A subgroup of 18 patients were found to have ultrasound (US) findings of polycystic ovaries (PCO). MAIN OUTCOME MEASURE: The amount of gonadotropin used, development of follicles greater than or equal to 14 mm, number of oocytes collected, fertilized, cleaved and replaced, serum and follicular fluid (FF) insulin-like growth factor I (IGF-I) concentrations. RESULTS: Cotreatment with GH was associated with a significant reduction in gonadotropins requirement (P less than 0.05). In patients with US-diagnosed PCO more follicles developed (P less than 0.05), more oocytes were collected (P less than 0.03), fertilized (P less than 0.004), and cleaved (P less than 0.02). A significantly higher FF IGF-I concentrations were found in patients receiving cotreatment with GH compared with those who received placebo (P less than 0.04). CONCLUSION: We believe that there may be a place for GH treatment in selected IVF cycles after pituitary suppression but what the role of IGF-I should further be investigated.