Luteal dysfunction in ovulation induction: the role of repetitive human chorionic gonadotropin supplementation during the luteal phase

Several studies have indicated that ovulation induction with human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) or clomiphene citrate (CC) is associated with luteal phase defect. To assess the efficiency of luteal support by hCG to an infertile population undergoing ovulation induction, with CC/hCG or hMG/hCG, we have randomly administered 2500 IU hCG intramuscularly on days 3, 6, and 9 after ovulation induction by 10,000 IU of hCG to 74 patients on 265 treatment cycles. As controls served 357 ovulation induction cycles in the same 74 patients. The treatment cycles were randomly alternated with control cycles so that each patient served as her own control. However, the mean +/- standard deviation (SD) midluteal P was 38.1 +/- 10.8 ng/ml in the study group versus 15.7 +/- 10.5 ng/ml in the control group (P less than 0.001). Luteal phase length was 15.4 +/- 1.5 days in the treatment group versus 12.1 +/- 1.7 in the control group (P less than 0.01). In the treatment group, 64.8% of the patients achieved pregnancy (27% pregnancies/treatment cycle) versus 47.3% in the control group (11.5% pregnancies/control cycle) (P less than 0.01). The pregnancy wastage rates (including abortions and "chemical" pregnancies) were 30.6% in the treatment group versus 56% in the control group (P less than 0.01). We conclude that repetitive hCG administration may be an efficient luteal support in infertile patients undergoing ovulation induction.     

The luteal phase in polycystic ovary syndrome during ovulation induction with human menopausal gonadotropin with and without leuprolide acetate

Little data exist on the effects of adjunctive therapy with leuprolide acetate (LA) in the luteal phase of women with polycystic ovary syndrome (PCOS) undergoing ovulation induction with human menopausal gonadotropin (hMG). Additionally, it is not known whether gonadal steroid concentrations in the luteal phase of induced cycles in PCOS are predictive of pregnancy. In this prospective, randomized study comparing cycles using hMG alone (n = 26) with cycles using hMG with LA (n = 33), no differences were noted between treatment groups in progesterone (P), estradiol (E2), and P:E2 ratios on luteal days 3, 6, and 9. When all treatment cycles were pooled, there were no differences in P, E2, or P:E2 ratios, comparing conception and nonconception cycles. We conclude that adjunctive therapy with LA in PCOS patients undergoing ovulation induction with hMG does not alter the luteal phase concentrations of P, E2, and P:E2. Furthermore, no correlation was found between the serum concentrations of these luteal phase steroids and cycle fecundity.     

Human chorionic gonadotropin, estradiol, and progesterone profiles in conception and nonconception cycles in an in vitro fertilization program

In 22 consecutive in vitro fertilization cycles stimulated with purified follicle-stimulating hormone, human chorionic gonadotropin (hCG), estradiol (E2), and progesterone (P) were measured every 3 days during the luteal phase. All serum measurements were normalized to the day of hCG administration (day 0). There was a total of nine pregnancies; two were biochemical pregnancies, whereas 7 of the 22 women had clinical pregnancies (31.8%). Of these, two miscarried and five had term pregnancies (three singleton, two twin). Conception cycles could be differentiated from nonconception cycles by serum E2 levels on day 8 (P = 0.035), by hCG levels on day 11 (P = 0.03), and by P levels on day 14 (P = 0.001). From days 8 to 11, hCG levels plateaued in conception cycles and decreased in nonconception cycles. However, during that period, E2 and P fell in both groups of women. This decline in sex steroids, which was observed in both conception and nonconception cycles, may well negatively influence endometrial development during the peri-implantation period and compromise conception, resulting in failure to conceive, biochemical pregnancy, and early miscarriage.     

Human menopausal gonadotropin/human chorionic gonadotropin follicular maturation for oocyte aspiration: phase I, 1981

Thirty-one human menopausal gonadotropin and human chorionic gonadotropin (hMG/hCG) ovulation induction cycles from 25 normally ovulating patients who applied to a program for the Vital Initiation of Pregnancy (VIP) are discussed. Three different categories of serum estradiol (E2) response were found. Serum E2 and progesterone responses were inversely related to the amount of hMG, indicating a patient sensitivity rather than a dosage relationship. Luteinizing hormone levels were suppressed by gonadotropins. Daily evaluation of vaginal smear, cervical mucus, serum E2 determinations, and pelvic ultrasound are necessary for an optimum ovulation induction with gonadotropins. Two successful pregnancies are reported.     

Comparison of human menopausal gonadotropin, clomiphene citrate, and combined human menopausal gonadotropin-clomiphene citrate stimulation protocols for in vitro fertilization

Human menopausal gonadotropins (hMG) and clomiphene citrate (CC), either alone or in combination, are frequently used for in vitro fertilization (IVF) in an attempt to maximize the number of oocytes recovered and the number of embryos transferred. However, direct comparison of the relative efficacy of these protocols in the same institution has been limited. To evaluate this question, the authors examined the outcome of 304 consecutive women attempting IVF. One hundred eighty-one women received hMG, 42 received CC, and 81 received combination hMG/CC. The percentages of women undergoing laparoscopy were not different among the groups (69%, 71%, and 74%, respectively), nor were the rates of oocyte recovery (94%, 100%, and 100%). However, the percentage of women achieving oocyte fertilization (77%, 83%, and 93%) and embryo transfer (73%, 83%, and 90%) were significantly greater among those who had received hMG/CC stimulation. A comparison of hMG/CC with hMG and CC cycles revealed a statistically significant increase in the total number of developing follicles (4.5 +/- 0.3, 3.3 +/- 0.2, and 3.1 +/- 0.3, respectively; P = 0.0137), total oocytes recovered (4.1 +/- 0.3, 3.2 +/- 0.2, and 2.5 +/- 0.2; P = 0.0011), and embryos transferred (2.2 +/- 0.2, 1.4 +/- 0.2, and 1.4 +/- 0.2; P = 0.0013). However, there was no significant difference in the occurrence of ongoing pregnancies. Thus, in terms of the per-patient number of follicles, oocytes, and embryo transfers, combined hMG/CC stimulation appears to be superior to either hMG or CC alone. However, to date the combined regimen has not improved pregnancy rates.     

Ovarian stimulation and corpus luteum function in human in vitro fertilization and embryo transfer

Ovarian stimulation and corpus luteum function in human in vitro fertilization and embryo transfer were investigated. Thirty-three cycles were treated with clomiphene citrate (CC) alone and 56 cycles with a CC/human menopausal gonadotropin (hMG) combination, and the latter was divided into three groups in the luteal phase; untreated (CC/hMG-NO) (n = 21), treated with progesterone (CC/hMG-P) (n = 23), and treated with human chorionic gonadotropin (hCG) (CC/hMG-hCG) (n = 12). There were many more increases in the number of aspirated follicles, recovered oocytes, and transferred embryos in the CC/hMG group than in the CC group. A significant correlation was found between the numbers of aspirated follicles and serum estradiol (E2) peaks in the follicular phase, and also between serum E2 peaks in the follicular phase and serum progesterone (P) maximum levels in CC and CC/hMG-NO. No significant difference was observed in serum P levels in the midluteal phase among four groups, though their levels were given in the following order; CC/hMG-hCG greater than CC/hMG-P greater than CC/hMG-NO. P/E2 ratios for the luteal phase in the CC/hMG-hCG group were significantly higher than those of other groups, but the pregnancy rate for the CC/hMG-hCG group was the lowest in the four groups. In conclusion, the high P and high P/E2 ratios following luteal treatment were not necessarily connected with pregnancy.     

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.     

Sonography of the endometrium during conception and nonconception cycles of in vitro fertilization and embryo transfer

The thickness of the endometrium was compared in 15 patients who conceived and 15 who did not with an in vitro fertilization and embryo transfer (IVF-ET) protocol after ovulation induction with human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG). There was no statistically significant difference (P = 1.0) in the endometrial thickness in the conception versus the nonconception group. Average estradiol (E2) values and number of mature follicles were also not statistically different in the two groups (P = 0.78, P = 0.81). There was a slightly significant difference in the number of embryos transferred in the conception versus nonconception groups (2.5 versus 1.9, P = 0.005). However, the most significant difference between the conception and nonconception groups was the total number of oocytes retrieved (4.4 versus 2.8, P = 0.005). These findings indicate that there are no sonographically detectable differences in the endometrial thickness in patients who achieve pregnancy versus those that do not when given a similar ovulation induction regimen of hMG/hCG for IVF-ET.     

Human menopausal gonadotropin/human chorionic gonadotropin follicular maturation for oocyte aspiration: phase II, 1981

Ovulation was induced in 24 cycles of normal ovulatory patients for in vitro fertilization using a modified human menopausal gonadotropin and human chorionic gonadotropin (hMG/hCG) protocol. This modification was based on experience in 31 cycles previously studied. The individual ovarian threshold response to hMG seen previously was again confirmed, and successful stimulation and oocyte retrieval depended upon the recognition of this patient's "sensitivity." A rapid serum estradiol (E2) assay, in conjunction with estimation of the patient's biologic response to the E2 levels, as measured by changes in vaginal smears and cervical mucus (biologic estrogen shift), was the key to determining the amount of hMG necessary. The biologic shift was the best indicator for discontinuation of gonadotropins in the low E2 responder group. The serum E2 levels were the best indicators for the normal and high E2 responder groups. Ultrasound was used as confirmatory evidence for satisfactory follicular development. Postmaturity of the oocyte did not occur in this series, due to compensation of excessive hMG stimulation in rapid responders by a shortening of the interval between hMG discontinuation and hCG administration, thus initiating the oocyte meiotic process earlier. Maturation of immature oocytes was accomplished in this series by an increase in the time in culture prior to insemination. Due to the improved protocol of drug administration and the ability to mature immature oocytes in vitro, five pregnancies resulted from the stimulation of these 24 cycles.     

Regulation of ovarian follicular and luteal function during treatment with exogenous gonadotropins in anovulatory infertility

The dosage, duration of treatment, and plasma hormone levels were analyzed statistically between and within groups of treatment cycles with (n = 46) and without (n = 10) ovulation. A significant difference was observed in the dosage of human menopausal gonadotropins (hMG) over various days of treatment, but not in the mean dosage of hMG and human chorionic gonadotropin (hCG) administered per cycle. Follicle-stimulating hormone (FSH):luteinizing hormone (LH) ratios, prolactin (PRL) levels, and the magnitude and the duration of the estradiol response were greater in the ovulatory cycles. Additionally, in the ovulatory cycles, the dose of hMG correlated with the plasma levels of estradiol, FSH, and LH, while in the anovulatory cycles, hMG dosage correlated only with the LH concentrations. After administration of hCG, the mean plasma concentrations of its beta subunit peaked within 1 day and remained detectable for up to 10 days thereafter. In the ovulatory cycles, the mean progesterone level was maximal 6 days following hCG administration. In these cycles, luteal phase progesterone levels correlated positively with the preovulatory estradiol and inversely with concentrations of the beta subunit of hCG. The data demonstrate that, in contrast to anovulatory follicles, ovulatory follicles were exposed to a relative "dominance" of FSH over LH, with higher concentrations of estradiol and PRL for several days before hCG was administered. Apart from hMG dosage, the endogenous discharge of LH appeared to be an important determinant of the ovarian response. A single 10,000 IU dose of hCG was adequate for inducing ovulation and maintaining luteal function.     

Relationship of follicle numbers and estradiol levels to multiple implantation in 3,608 intrauterine insemination cycles

OBJECTIVE: To determine the relationship of follicle numbers and estradiol (E(2)) levels to multiple implantations in human menopausal gonadotropin (hMG) and clomiphene citrate (CC) cycles. DESIGN: Fifteen-year prospective study. SETTING: Private infertility clinic. PATIENT(S): Women who underwent 3608 cycles of husband or donor intrauterine insemination (IUI). INTERVENTION(S): Ovulation induction (OI) with CC, hMG, or CC+hMG. MAIN OUTCOME MEASURE(S): Pregnancy and multiple implantations. RESULT(S): Triplet and higher-order implantations-but not twin implantations-were related to age, E(2) levels, and number of follicles > or = 12 mm and > or = 15 mm, but not number of follicles > or = 18 mm, in hMG and CC+hMG cycles. For patients less than 35 years old, three or more implantations tripled when six or more follicles were > or = 12 mm, in CC, hMG, and CC+hMG cycles, and when E(2) was > or = 1000 pg mL in hMG and CC+hMG cycles. For patients 35 or older, pregnancy rates in hMG and CC+hMG cycles doubled when six or more follicles were > or = 12 mm, or E(2) levels were >1000 pg mL, whereas 3 or more implantations were not significantly increased. CONCLUSIONS: Withholding hCG or IUI in CC, hMG, and CC+hMG cycles when six or more follicles are > or = 12 mm may reduce triplet and higher-order implantations by 67% without significantly reducing pregnancy rates for patients under 35 years of age.     

Premature luteinizing hormone surges in menopausal gonadotropin-stimulated cycles in monkeys: lack of initiation by progesterone

The occurrence of spontaneous luteinizing hormone (LH) surges in women receiving human menopausal gonadotropins (hMG) for in vitro fertilization-embryo transfer is a significant clinical problem. One hypothetical mechanism is that premature progesterone (P) secretion occurring in the high estradiol (E2) milieu produced by hMG triggers the spontaneous LH surge. To investigate this possibility, 11 rhesus and cynomolgus monkeys were stimulated with hMG. At maximal ovarian stimulation, monkeys were injected with 15 micrograms/kg P (n = 3), 30 micrograms/kg P (n = 3), or 1,000 IU human chorionic gonadotropin (hCG) (n = 5; controls). Blood for E2, P, and LH was drawn twice daily in the periovulatory period and daily before and after this period. Laparoscopy was performed after P or hCG injection. In the 6 monkeys receiving P, no LH surges were detected. Further, postinjection P profiles and laparoscopy showed no evidence of ovulation. Controls demonstrated laparoscopic and hormonal evidence of ovulation. These findings suggest that P does not trigger LH surges in hMG-stimulated cycles.     

The luteal phase during gonadotropin therapy: effects of two human chorionic gonadotropin regimens

OBJECTIVE: Luteal phase abnormalities are known to complicate ovulation induction with gonadotropins. This study was performed to test the effect of a modified human chorionic gonadotropin (hCG) regimen on the luteal phase during gonadotropin treatment. DESIGN: Fifteen women from a private practice setting volunteered to be studied during each of two nonconception, gonadotropin-stimulated cycles. After ovarian stimulation with human menopausal gonadotropins (hMG), hCG was administered either as a single dose of 10,000 IU (single dose) or in two divided doses of 5,000 IU given 1 week apart (split dose). MAIN OUTCOME MEASURES: Early, midluteal, and late luteal estradiol (E2) and progesterone (P) levels and luteal phase lengths were measured, and their median values and intraquartile ranges (IQR) compared using nonparametric analysis. RESULTS: Early and midluteal E2 and P levels were similar regardless of which hCG regimen was administered. The median late luteal E2 level was 1,146.0 pg/mL (the IQR ranged from 633 to 1,650, IQR = 1,017) with the split-dose regimen and 240.0 pg/mL (the IQR ranged from 150 to 460, IQR = 310) with the single-dose regimen. The median late luteal P level was 108.0 ng/mL (the IQR ranged from 58.5 to 129, IQR = 70.5) with the split-dose regimen and 4.2 ng/mL (the IQR ranged from 1.9 to 11.7, IQR = 9.8) with the single-dose regimen. Median luteal phase lengths were 16 days (the IQR ranged from 15 to 17, IQR = 2) for the split-dose regimen and 11 days (the IQR ranged from 10 to 12, IQR = 2) for the single-dose regimen. CONCLUSION: In hMG-stimulated cycles, a second dose of hCG given during the midluteal phase significantly increases late luteal E2 and P levels and consistently lengthens the luteal phase.     

自然及促排卵周期子宫内膜整合素α4β1的表达

目的 了解氯米芬（CC）、绝经期促性腺激素（hMG）对黄体中期子宫内膜整合素α4β1表达的影响。方法 应用单克隆抗体,采用免疫组织化学技术检测48例正常妇女自然周期以及48例正常妇女、30例多囊卵巢综合征患者应用CC／绒毛膜促性腺激素（hCG）及CC／hMG/hCG方案促卵治疗后黄体中期子宫内膜整合素α4β1的表达。结果 子宫内膜整合素α4β1在正常妇女自然周期着床窗口期呈现强阳性表达,而CC、hMG抑制整合率α4β1的表达,两者比较,差异有极显著性（P＜0．01）;妊娠者较妊娠者整合素α4β1表达强度高。结论 促排卵周期黄体中期整合素α4β1表达下降或缺失,子宫内膜容受性下降,妊娠率降低。     

Prevention of premature luteinizing hormone and progesterone rise with a gonadotropin-releasing hormone antagonist, Nal-Glu, in controlled ovarian hyperstimulation

OBJECTIVE: To report a preliminary study on the efficacy of a gonadotropin-releasing hormone antagonist (Nal-Glu) for preventing premature luteinizing hormone (LH) and progesterone (P) rise in controlled ovarian hyperstimulation using clomiphene citrate (CC) and human menopausal gonadotropin (hMG). DESIGN: Participants in the study formed two groups. Both groups received CC-hMG and Nal-Glu. Group II differs from group I for receiving human chorionic gonadotropin (hCG) and blood samples for 10 days after the second Nal-Glu injection. SETTING: Centre de Fecondation in Vitro, H?pital Antoine Béclère. PATIENTS: Eleven women 25 to 34 years of age and having normal menstrual cycles using barrier method of contraception not attempting pregnancies participated in the study. INTERVENTION: Daily blood samples, pelvic ultrasound, and CC-hMG/Nal-Glu/hCG administration. MAIN OUTCOME MEASURES: (1) Spontaneous LH surge and P rise, follicular growth, and plasma E2 levels in cycles with CC-hMG/Nal-Glu administration and (2) luteal phase after hCG injection in subjects previously treated with CC-hMG/Nal-Glu. RESULTS: Plasma E2 level increased from 983 +/- 80 pg/mL (mean +/- SEM) on the day of the first Nal-Glu administration to 1,159 +/- 102 and 1,610 +/- 114 pg/mL (mean +/- SEM) 24 and 48 hours later. In 10 women, LH and P remained low for at least 96 hours after the first Nal-Glu administration. In one subject, plasma LH was already elevated at the time of the first Nal-Glu injection. In women who received hCG, plasma E2 and P reached a maximum of 1,258 +/- 313 pg/mL and 50.3 +/- 12.8 ng/mL (mean +/- SEM), respectively, on the 6th day of the luteal phase. CONCLUSION: Our results suggest that timely Nal-Glu injections can prevent LH and P rise for at least 96 hours, in spite of increasing levels of plasma E2. Moreover, Nal-Glu had no adverse effect on the kinetic of E2 rise, the follicular growth, or on the post-hCG hormonal profile.     

A prospective, randomized trial comparing two different intrauterine insemination regimens in controlled ovarian hyperstimulation cycles.

OBJECTIVE: To compare a single periovulatory intrauterine insemination (IUI) with a regimen employing two IUIs, one before ovulation and one after ovulation, in patients undergoing controlled ovarian hyperstimulation with human menopausal gonadotropins (hMG) combined with human chorionic gonadotropin (hCG). DESIGN: A randomized, prospective trial. PARTICIPANTS: Thirty-one consecutive patients undergoing 49 cycles of controlled ovarian hyperstimulation/IUI were studied in a tertiary care setting. MAIN OUTCOME MEASURES: Ovulation was determined sonographically. The establishment of a clinical pregnancy was defined by either ultrasonographic verification of cardiac activity within an intrauterine fetus, or histologic confirmation of trophoblast in a surgical specimen. RESULTS: Clinical pregnancies developed in 2 of 23 cycles in the single insemination group, compared with 12 of the 23 cycles in the double insemination group. Cycle fecundity was significantly higher for group II (0.522) than for group I (0.087) patients (P = 0.003). CONCLUSION: In hMG/hCG cycles, two IUIs timed as described above are superior to one periovulatory insemination.     

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.     

Ultrasonographic and clinical correlates of menotropin versus sequential clomiphene citrate: menotropin therapy for induction of ovulation

Forty-six women remaining infertile with clomiphene citrate (CC) with or without human chorionic gonadotropin (hCG) were treated by either human menopausal gonadotropin (hMG, 44 cycles) or CC + hMG (33 cycles) and monitored by serum estradiol (E2) and ultrasonography. Ovarian hyperstimulation syndrome (OHS) and pregnancy outcome were compared in both regimens. In the presence of dominant follicles (greater than or equal to 18 mm) alone or with a single secondary follicle (14 to 16 mm) at hCG administration, OHS did not develop. A significant increase in OHS was noted when three or more secondary follicles were observed. Overall pregnancy rates were similar in both regimens but significantly higher when hCG was injected before rather than after the E2 peak. The results suggest secondary follicles rather than dominant follicles are a valuable sign of possible OHS development; and CC + hMG should be considered in CC-failure patients.     

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.     

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.