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.     

Ovulation induction using "pure" follicle-stimulating hormone in monkeys

Recently we have demonstrated that administration of a "pure" follicle-stimulating hormone (FSH) preparation (Urofollitropin, Serono Laboratories, Inc., Randolph, MA) to normally cycling monkeys induces multiple follicular development. In these earlier studies, a spontaneous luteinizing hormone (LH) surge was uncommon; no attempt was made to induce ovulation with exogenous human chorionic gonadotropin (hCG). In this study, multiple follicular development and ovulation were induced in normally cycling monkeys by daily follicular phase administration of "pure" FSH followed by hCG. Short-term administration of "pure" FSH during the early or late follicular phase also induced multiple follicular development; however, multiple ovulations subsequent to a spontaneous LH surge never occurred. One monkey treated in the late follicular phase did demonstrate a spontaneous LH surge and single ovulation following late follicular phase FSH treatment. These findings suggest that administration of "pure" FSH alone, to enhance the natural ovarian cycle, may be useful for inducing multiple follicular development, but that ovulatory competence is usually dependent on exogenous LH/hCG.     

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.     

Short-term use of gonadotropin-releasing hormone agonist (Leuprolide) for in vitro fertilization

A common problem encountered by in vitro fertilization (IVF) programs is the premature occurrence of the spontaneous lutenizing hormone (LH) surge during ovarian stimulation cycles. Administration of gonadotropin-releasing hormone agonists (GnRH-a) for 2 to 3 weeks produces a state of hypogonadotropic hypogonadism, thus allowing ovarian stimulation to proceed uncomplicated by a spontaneous LH surge. We have elected to treat seven patients with GnRH-a in a short-term protocol, with GnRH-a initiated on cycle day 3 along with exogenous gonadotropins. In this series, we found that the spontaneous LH surge was abolished, while ovarian responsiveness seemed to be improved. These results suggest that the initial surge of gonadotropins elicited by GnRH-a administration may enhance ovarian stimulation and that spontaneous LH surge is blocked when GnRH-a and exogenous gonadotropins are initiated concomitantly.     

Variations of luteinizing hormone serum concentrations after exogenous human chorionic gonadotropin administration during ovarian hyperstimulation

Changes in luteinizing hormone (LH), estradiol, and progesterone (P) serum levels before and after preovulatory administration of human chorionic gonadotropin (hCG) were assayed in 30 patients stimulated with clomiphene citrate (CC) and human menopausal gonadotropin (hMG) and compared with LH variations in 43 patients submitted to pharmacological hypophysectomy with a gonadotropin-releasing hormone agonist (GnRH-a) and stimulation with hMG. In CC + hMG-treated patients, an endogenous LH surge occurred systematically 4.25 +/- 2.75 hours after hCG injection. Multiparametric analysis indicated an inverse correlation between the delay in the initial rise of the LH surge and the increase in P levels during the 6 hours after hCG administration. Gonadotropin-releasing hormone agonist + hMG treatment did not lead to an LH surge after hCG but to a significant fall in LH levels. Thus, exogenous hCG, administered before ovulation, induces an endogenous LH surge if pituitary function is not blocked by a GnRH-a, probably through an increase in P secretion.     

Prospective study of short and ultrashort regimens of gonadotropin-releasing hormone agonist in an in vitro fertilization program.

OBJECTIVE: To assess the usefulness of the ultrashort regimen of gonadotropin-releasing hormone agonist (GnRH-a) in ovulation induction in an in vitro fertilization (IVF) program. DESIGN: A prospective randomized trial comparing short and ultrashort regimens of GnRH-a. SETTING: Aberdeen Assisted Reproduction Unit. PATIENTS: Forty-eight patients having IVF for the first time were randomized between the two protocols. MAIN OUTCOME MEASURES: Response to ovarian stimulation and occurrence of spontaneous luteinizing hormone (LH) surges. RESULTS: In ovulation induction, fertilization, and pregnancy rates the ultrashort regimen produces results that were no different to the short regimen but it did not always prevent an LH surge. CONCLUSION: The ultrashort regimen can be a useful alternative for ovarian stimulation of patients undergoing IVF.     

The effect of follicle-stimulating hormone without additional luteinizing hormone on follicular stimulation and oocyte development in normal ovulatory women

Twelve normally menstruating women were stimulated with (1) human menopausal gonadotropins (hMG) containing follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and (2) FSH only to induce growth of multiple follicles for oocyte retrieval. Maturation of the follicles and presumptively the oocytes was assessed by daily serum estradiol (E2) values, the response of the vaginal epithelium, and cervical mucus. The growth and number of follicles were measured by ultrasound daily. Human chorionic gonadotropin was administered as a surrogate LH surge. The hMG cycles were compared with the FSH-only cycles in relation to serum E2 and oocyte maturation, fertilization, transfer, and pregnancy rates. Five of eight cycles adequately stimulated with FSH only resulted in successful pregnancies. FSH without additional LH can initiate and maintain E2 function and allow oocyte maturation to proceed up to the terminal maturation, which is associated with the LH surge. The effect of LH may be to hasten follicular atresia in the developing cohort of follicles.     

A prospective randomized comparison between long and discontinuous-long protocols of gonadotropin-releasing hormone agonist for in vitro fertilization

Objective: To investigate the efficacy of a discontinuous-long protocol in an IVF program.

Design: Prospective randomized study.

Setting: University hospital.

Patient(s): One hundred thirty-seven IVF cycles of 92 patients in an outpatient IVF program from April 1995 to December 1995.

Intervention(s): In the discontinuous-long protocol group (n = 68), GnRH agonist (GnRH-a) was administered from the luteal phase until cycle day 7, when pure FSH administration was begun. In the long protocol group (n = 69), GnRH-a was administered until the day before hCG administration.

Main Outcome Measure(s): Serum LH and ovarian steroid hormone levels, and IVF outcome.

Result(s): The period and the total dosage of hMG were increased in the discontinuous-long protocol group. Although the fertilization rate was similar under both protocols, the number of embryos transferred was smaller and the cancellation rate was higher in the discontinuouslong protocol group because of the greater failure of oocyte retrieval and fertilization. Serum E₂ levels in the late follicular phase were lower in the discontinuous-long protocol group.

Conclusion(s): Early discontinuation of GnRH-a is not beneficial because of its adverse effects on follicular development.     

Ovarian hyporesponsiveness in combined gonadotropin-releasing hormone agonist and menotropin therapy is associated with low serum follicle-stimulating hormone levels.

The study was designed to evaluate if ovarian hyporesponsiveness, which is associated with combined gonadotropin-releasing hormone agonist (GnRH-a) and human menopausal gonadotropin (hMG) therapy is because of suboptimal serum follicle-stimulating hormone (FSH) levels. Two groups of 12 patients each were suppressed with GnRH-a and stimulation with a fixed dose of hMG. The control group (n = 10) received equal doses of hMG only. The follicular phase and the number of hMG ampules was significantly higher in the study group. Basal FSH levels and FSH levels during hMG treatment were significantly lower in patients treated with GnRH-a. Peak estradiol levels and the outcome of in vitro fertilization treatment were similar in the three groups. We suggest that the delay in ovarian response in patients treated with a combination of GnRH-a and hMG is because of lack of endogenous contribution of FSH, resulting in low circulating levels of FSH. An increase of serum FSH levels by administration of higher doses of hMG can reverse this effect.     

IVF-ET中促性腺激素释放激素激动剂的超促排卵应用与剂量研究

促性腺激素释放激素激动剂(GnRH-a)是体外受精-胚胎移植(IVF-ET)技术中重要用药。GnRH-a与GnRH受体结合后,早期"突发"作用可刺激垂体促性腺激素急剧释放,持续应用后使垂体受抑制,内源性促性腺激素(Gn)水平下降,即所谓的降调节作用。利用这种生物学特性,GnRH-a联合Gn超促排卵可预防早发黄体生成素(LH)峰,避免卵泡过早黄素化。另外,GnRH-a代替人绒毛膜促性腺激素诱发排卵可降低卵巢过度刺激综合征(OHSS)发生率。探索既能有效抑制LH峰,又不使垂体过度抑制的GnRH-a有效低剂量对于超促排卵有重要意义。     

In vitro fertilization: diurnal and seasonal variation in luteinizing hormone surge onset and pregnancy rates

The authors studied 740 consecutive in vitro fertilization (IVF) cycles over a 3-year period to compare the results of cycles in which an endogenous luteinizing hormone (LH) surge occurred with cycles in which human chorionic gonadotropin (hCG) was administered for induction of follicular maturation. Clomiphene citrate (100 to 150 mg daily on cycle days 5 to 9) and human menopausal gonadotropin (hMG; 75 to 150 IU daily from cycle day 6) were used for stimulation. Embryo transfer (ET) occurred in 164 (81.2%) of the LH surge cycles and 452 (84%; P = not significant [NS] of the hCG cycles. The first urinary rise in LH was detected in the 6 or 9 A.M. collections in 78 (47.3%) of the LH surge cycles, a greater number (P less than 0.01) than expected if LH surge onset was random. A total of 107 pregnancies was achieved, for an overall pregnancy rate of 17.4% per ET. The pregnancy rate in the hCG-stimulated cycles was 13.9% per ET (63/452) and, in spontaneous LH surge cycles, was 28.8% (44/166; P less than 0.001). The spontaneous abortion rate was 9.1% in LH surge cycles, compared with 25.4% in hCG-triggered cycles (P less than 0.001). The result was a 2.4 times increase in live births for LH surge cycles compared with cycles in which hCG was administered. In this program, occurrence of an LH surge is a favorable event, associated with higher pregnancy and live birth rates than hCG-stimulated cycles, and usually occurring in the early morning, allowing oocyte retrieval during normal working hours.     

Hemodynamic changes induced by urinary human chorionic gonadotropin and recombinant luteinizing hormone used for inducing final follicular maturation and luteinization

OBJECTIVE: To compare the safety of recombinant human luteinizing hormone (LH) with that of urinary hCG in terms of the hemodynamic changes when they are used to induce final follicular maturation in patients undergoing in vitro fertilization (IVF). A secondary end point was efficacy in terms of IVF outcome. DESIGN: Prospective, randomized clinical trial. SETTING: University teaching hospital. PATIENT(S): Thirty IVF patients. INTERVENTION(S): Ovarian stimulation was induced with FSH under pituitary suppression. Patients were randomized to receive either hCG or recombinant human LH as a trigger of oocyte maturation (5,000 IU) and for luteal phase support (5,000 IU, 2,500 IU, and 2,500 IU on the day of follicular aspiration, 2 days later, and 5 days later, respectively). MAIN OUTCOME MEASURE(S): Mean arterial pressure, cardiac output, peripheral vascular resistance, and serum levels of progesterone, plasma concentrations of aldosterone, norepinephrine, and plasma renin activity were measured in all patients on postovulatory day 7 of the spontaneous menstrual cycle preceding IVF (baseline) and 7 days after the hCG/recombinant human LH ovulatory injection during the IVF cycle. RESULT(S): Ovarian response and IVF outcome (pregnancy rate, 60%) were similar in both treatment groups. On the seventh day after hCG/recombinant human LH administration, the peripheral vascular resistance was significantly lower and serum progesterone concentrations significantly higher in the hCG group as compared with the recombinant human LH group. The percentage change from baseline values during IVF cycles in all hemodynamic and neurohormonal variables investigated was higher (albeit not statistically different) in the group treated with hCG vs. the group treated with recombinant human LH. CONCLUSION(S): Recombinant human LH is associated with less intense circulatory changes than hCG when it is given to induce final follicular maturation and luteal phase support in IVF procedures.     

Follicular development and oocyte maturation after stimulation with gonadotropins versus leuprolide acetate/gonadotropins during in vitro fertilization

Follicular development and oocyte maturation were compared in 22 patients stimulated with human menopausal gonadotropins/human chorionic gonadotropin (hCG, group I) and in 52 women also treated with the gonadotropin-releasing hormone agonist (GnRH-a) leuprolide acetate (LA, group II). Suppression of endogenous leutinizing hormone (LH) surges by LA allowed delayed hCG administration, resulting in higher peripheral estradiol levels, more retrieved oocyte cumulus corona complexes, and greater numbers of cryopreserved embryos. Reduction in spontaneous LH surges in the GnRH-a cycles may have allowed time for larger follicular fluid (FF) volume accumulation during all phases of oocyte cumulus corona complex maturation, restoring synchrony between FF volume and oocyte cumulus corona complex maturity.     

The role of endogenous gonadotropin release in the etiology of ovarian enlargement during purified urinary follicle-stimulating hormone therapy

Patients with polycystic ovarian disease were grouped into three groups according to their maximum ovarian diameter (maxD) after ovulation induction by purified urinary follicle-stimulating hormone (FSH). Serum luteinizing hormone (LH) and FSH were measured daily by radioimmunoassay and size and number of follicles were assessed by ultrasonography. Follicle-stimulating hormone in group A (80 mm less than or equal to maxD) was significantly higher than those of group B (60 mm less than or equal to maxD less than 80 mm) and C (maxD less than 60 mm) for the last 4 days of the treatment. This FSH rise in group A was not accounted for by FSH accumulation by the study of pharmacodynamics, and so was thought to be of endogenous origin. Luteinizing hormone was also elevated 3 days before the administration of human chorionic gonadotropin (hCG) in both groups A and B. The number of follicles in group A at hCG administration was significantly greater than that of group C. Any significant differences were not found in either total amount of purified urinary FSH or in the basal FSH and the LH levels before treatment of the three groups. These results suggest that excessive ovarian enlargement during gonadotropin therapy is caused by multiple follicular development primarily stimulated by endogenous FSH. Endogenous LH release further enhances ovarian enlargement.     

Prospective randomized study of human menotropin versus a follicular and a luteal phase gonadotropin-releasing hormone analog-human menotropin stimulation protocols for in vitro fertilization

OBJECTIVE: To determine whether gonadotropin-releasing hormone analogs (GnRH-a) initiated either in the luteal phase or in the early follicular phase immediately preceding menotropin will improve the fertilization, implantation, and pregnancy rates (PR) in all IVF patients, when compared with menotropins alone. DESIGN: In a prospective, controlled, randomized study we compared a pure follicle-stimulating hormone (FSH) human menopausal gonadotropin (hMG) protocol (group A = control) (n = 93 cycles) to two protocols in which GnRH-a pretreatment plus pure FSH and/or hMG was used in in vitro fertilization candidates. In group B (n = 64) GnRH-a was initiated during the luteal phase and in group C (n = 35) during the follicular phase. RESULTS: We found (1) no differences in fertilization and implantation rates between the three protocols; (2) similar pregnancy rates per transfer when similar number of conceptus were transferred (A = 30%, B = 22%, C = 21%); (3) an increase of the number of oocytes obtained; and (4) a reduction in the cancellation rate with both GnRH-a protocols. CONCLUSIONS: These findings suggest that there is no obvious superiority between the two GnRH-a protocols in the dosage schedule used and that the major advantage of GnRH-a over non-GnRH-a protocols is in decreasing the cancellation rate and increasing the number of oocytes and conceptus obtained. The follicular phase GnRH-a protocol required less hMG-pure FSH than the luteal phase GnRH-a protocol.     

基础FSH/LH比值及晚卵泡期LH水平对体外受精-胚胎移植结局的影响

目的:探讨患者基础FSH/LH比值及控制性超促排卵(COH)时降调后hCG注射日血清LH水平对IVF-ET结局的影响及与COH各参数的关系。方法:回顾性分析首次进行IVF/ICSI-ET助孕、应用GnRH-a长方案降调节的不孕妇女,共427个周期。结果:ROC曲线显示FSH/LH比值与IVF-ET临床妊娠率无明显相关性;FSH/LH≥2与FSH/LH<2组间虽然临床妊娠率无差异,但FSH/LH≥2组Gn用量增加,获卵数少,优质胚胎数少,存在统计学差异(P<0.05)。hCG注射日血清LH≥0.65IU/L者妊娠率(55.8%)明显高于LH<0.65IU/L者(24.6%)。结论:基础FSH/LH比值增高能较早反映卵巢储备功能并指导超排方案及Gn用量;降调节后卵泡晚期(hCG注射日)的LH水平过低(<0.65IU/L),将会导致临床妊娠率下降。     

Clomiphene-HMG ovarian stimulation in human in vitro fertilization and embryo transfer

In a program for in vitro fertilization and embryo transfer, laparoscopies for oocyte aspiration were performed in 40 cycles in 36 normally menstruating women with irreparable tubal diseases (IVF patients) who received clomiphene citrate (CC) and human menopausal gonadotropin (hMG). An intramuscular injection of human chorionic gonadotropin (hCG) was given to all patients after completion of follicular maturation. Fourteen cycles in 13 spontaneously ovulating women (control patients), also stimulated with CC and hMG, were adequately monitored to identify the appearance of the spontaneous luteinizing hormone (LH) surge. The follicular maturation was followed by daily ovarian ultrasonographic examination and serum estradiol estimations. Just before the LH surge the diameter of the leading follicle was 20.2 +/- 0.7 (mean +/- S.E.) mm and the serum estradiol concentration per follicle was 384.1 +/- 16.3pg/ml in the control patients. In the IVF patients the former was 20.6 +/- 0.3mm and the latter was 305.8 +/- 13.3pg/ml prior to hCG administration. When the relationship of follicular size to the rates of oocytes recovery, maturation, fertilization and cleavage was examined, larger follicles (3ml less than or equal to follicular fluid volume) showed good results. Of the 152 oocytes that were recovered from these IVF patients, 96 (63.2%) were fertilized and 79 (52.0%) cleaved. Three pregnancies resulted from 35 embryo transfers.     

Effects of low day 3 luteinizing hormone levels on in vitro fertilization treatment outcome.

In a previous study we demonstrated that women with day 3 luteinizing hormone (LH) values < 3 IU/l subjected to controlled ovarian hyperstimulation without pituitary desensitization responded with a lower number of follicles > 15 mm compared to women with a higher basal LH level. The aim of this study was to determine whether in patients with day 3 LH levels < 3 IU/l a further reduction of serum LH concentration by gonadotropin-releasing hormone (GnRH) analog impairs follicular response to follicle stimulating hormone (FSH) and treatment outcome in in vitro fertilization (IVF) cycles. For this purpose we retrospectively studied 249 consecutive women subjected to standard IVF treatment employing pituitary desensitization with buserelin and follicular stimulation with urinary highly purified FSH. The patients were divided into two groups according to their day 3 LH value. The first group (group A) showed day 3 LH levels < 3 IU/l and the second (group B) had day 3 LH levels > 3 IU/l. Group A and B patients did not show statistically significant differences in the ovarian response to FSH, nor in IVF treatment outcome, showing that in FSH treated GnRH analog suppressed cycles, the ovarian responsiveness and IVF outcome do not differ according to basal LH values. However, the high dosage of FSH we employed in group A and B patients could account, at least in part, for this result. Indeed, comparative evaluations with unsuppressed cycles (our previous study) strongly suggest that a reduced ovarian responsiveness to gonadotropins in patients with day 3 LH values < 3 IU/l should be considered in clinical practice.     

Gonadotropin-releasing hormone agonist versus human chorionic gonadotropin for triggering follicular maturation in in vitro fertilization.

OBJECTIVE: To compare the use of gonadotropin-releasing hormone agonist (GnRH-a) with human chorionic gonadotropin (hCG) for triggering the final stage of follicular maturation for in vitro fertilization (IVF). DESIGN: In vitro fertilization outcome was determined in a randomized, prospective study. SETTING: The University of Toronto IVF program at The Toronto Hospital, Toronto General Division. PATIENTS AND INTERVENTIONS: One hundred seventy-nine women in the IVF program were given a subcutaneous injection of leuprolide acetate (500 micrograms) or an intramuscular injection of hCG (5,000 IU) 34 to 36 hours before oocyte retrieval. Vaginal progesterone (P) suppositories (50 mg) were used two times a day for luteal phase support. A subgroup of 41 women had serum estradiol (E2) and P levels determined 2 and 7 days after embryo transfer (ET). MAIN OUTCOME MEASURES: Pregnancy rates and luteal phase E2 and P were compared. RESULTS: In the GnRH-a group, there were 18 pregnancies from 84 ETs (20%). In the hCG group, there were 19 pregnancies from 95 ETs (19%). Luteal phase E2 and P levels were significantly lower in the GnRH-a group compared with the hCG group, and 18% of the former group had an apparent short luteal phase. CONCLUSIONS: Gonadotropin-releasing hormone agonist appears to be an effective alternative to hCG for inducing follicular maturation in IVF. The lower luteal phase E2 concentrations may potentially be beneficial in preventing ovarian hyperstimulation and for enhancing implantation. Better luteal phase support or a different dose of GnRH-a is needed to prevent luteal phase deficiency.     

Follicular atresia associated with concurrent initiation of gonadotropin-releasing hormone agonist and follicle-stimulating hormone for oocyte recruitment

The ability of gonadotropin-releasing hormone agonist (GnRHa) to cause an initial stimulation of serum gonadotropins was used for follicular recruitment for in vitro fertilization (IVF) in 12 patients with a history of low estradiol (E2) response to conventional gonadotropin stimulation. Stimulation was initiated on cycle day 3 with concurrent administration of leuprolide (1 mg/day subcutaneously) and follicle stimulating hormone (FSH, 4 ampules/day intramuscularly). An 8-fold increase in basal serum luteinizing hormone (LH) and a 4-fold increase in basal serum FSH was seen on cycle day 4. Serum progesterone levels rose significantly by day 6. When compared to prior IVF attempts in these patients, the mean day of human chorionic gonadotropin administration and corresponding E2 levels were not significantly different. More atretic oocytes and fewer preovulatory oocytes were retrieved using GnRHa, and no increase was seen in total oocytes retrieved. One patient was canceled for poor E2 response, and one patient conceived, with a current viable pregnancy. It is concluded that concurrent initiation of leuprolide and FSH stimulation on cycle day 3 in patients with prior low response does not improve oocyte recruitment, and the high LH environment generated from initial stimulation of the agonist may be detrimental to normal oocyte development.