Follicular phase serum levels of luteinizing hormone do not influence delivery rates in in vitro fertilization cycles down-regulated with a gonadotropin-releasing hormone agonist and stimulated with recombinant follicle-stimulating hormone

OBJECTIVE: To assess the value of serum LH measurements in early and late follicular phase as predictors of ovarian response and IVF outcome in patients treated with recombinant FSH with GnRH agonist (GnRH-a) pituitary down-regulation. DESIGN: Retrospective cohort analysis. SETTING: Institutional. PATIENT(S): Women undergoing 157 consecutive IVF cycles suppressed with leuprolide acetate (LA) started in the midluteal phase and stimulated with recombinant FSH. Only women <40 years of age and with a basal cycle day 3 serum FSH 相似文献   

Recombinant follicle-stimulating hormone versus human menopausal gonadotropin in the late follicular phase during ovarian hyperstimulation for in vitro fertilization

OBJECTIVE: To study the effect of exogenous LH in the late follicular phase on ongoing pregnancies and at the different stages of IVF-ET (stimulation, fertilization, and implantation) in patients with low endogenous LH. DESIGN: Retrospective cohort study with modeling of the different phases of IVF-ET. SETTING: IVF center of the teaching hospital in Bordeaux, France. PATIENT(S): Women undergoing IVF and ICSI treatment. INTERVENTION(S): One group received recombinant FSH alone (FSH group) and the other received recombinant FSH and hMG in the late follicular phase (i.e., when the largest follicle reached 14 mm) (FSH/hMG group). MAIN OUTCOME MEASURE(S): Ongoing pregnancy, number of oocytes, and number of embryos.RESULT(S): The FSH/hMG group had a higher probability of having at least one oocyte (odds ratio [OR] = 2.75 [1.11-6.80]), of having at least one embryo after oocyte retrieval (OR = 2.84 [1.33-6.07]), and of ongoing pregnancy after ET (OR = 2.04 [0.83-5.01]), and globally had a higher probability of ongoing pregnancy (OR = 2.83 [1.19-6.71]). CONCLUSION(S): In ovarian hyperstimulation for IVF-ET, LH supplementation in the late follicular phase of women with low endogenous LH is beneficial for ongoing pregnancy by increasing the rate of success of all stages of the treatment.     

Effect of clomiphene citrate on follicular and luteal phase luteinizing hormone concentrations in in vitro fertilization cycles stimulated with gonadotropins and gonadotropin-releasing hormone antagonist

OBJECTIVE: To investigate the effect that clomiphene citrate exerts on luteinizing hormone (LH) concentrations in gonadotropin/gonadotropin-releasing hormone (GnRH) antagonist cycles. DESIGN: Retrospective analysis. SETTING: Tertiary referral center. PATIENT(S): Two groups of patients undergoing in vitro fertilization (IVF) were compared. In group I, 20 patients were stimulated with clomiphene citrate (CC) in combination with gonadotropins and 0.25 mg of Cetrorelix (ASTA Medica AG; Frankfurt am Main, Germany) and in group II, 20 patients were stimulated with gonadotropins and 0.25 mg of Cetrorelix. INTERVENTION(S): Blood sampling was performed in the late follicular, periovulatory, early, mid, and late luteal phases. MAIN OUTCOME MEASURE(S): Luteinizing hormone (LH), estradiol, and progesterone. RESULT(S): LH levels were significantly higher in group I than in group II on all the days studied. Progesterone serum concentrations were significantly higher in group II in the early luteal phase, but not in the follicular or the middle and late luteal phases. CONCLUSION(S): LH concentrations are significantly higher in the follicular and luteal phases in cycles stimulated with CC, despite GnRH antagonist administration. This observation might have implications for the dose of GnRH antagonist needed to suppress LH in the follicular phase and questions the need for luteal-phase supplementation in cycles in which CC was used.     

Follicular fluid concentrations of interleukin-12 and interleukin-8 in IVF cycles

OBJECTIVE: To investigate the role of interleukin-12 (IL-12) and IL-8 in the periovulatory follicular fluid during in vitro fertilization cycles. DESIGN: A prospective study. SETTING: Reproductive Medicine Unit, Liverpool Women's Hospital, United Kingdom. PATIENT(S): Women undergoing in vitro fertilization treatment. INTERVENTION(S): IL-8 and IL-12 concentrations in follicular fluid samples that had been collected during transvaginal oocyte retrieval were measured using an enzyme-linked immunosorbent assay (ELISA). Cytokine concentrations were correlated to fertilization rates and treatment outcome. MAIN OUTCOME MEASURE(S): Fertilization rates and ultrasonographic evidence of intrauterine pregnancy by 4 weeks after embryo transfer. RESULT(S): Failed fertilization in women with detectable IL-12 was significantly higher (45.5%) than in the IL-12 negative group (6.1%), P=.01. None of the women with detectable IL-12 achieved a pregnancy at the end of the treatment (P=.01). IL-8 was present in the follicular fluid of all women, and no difference in its concentrations was found between the pregnant and nonpregnant groups. No correlation was found between the follicular fluid concentrations of IL-8 and fertilization rates. CONCLUSION(S): The presence of IL-12 in the follicular fluid appears to be associated with a negative outcome in IVF treatment. Interleukin-8 appears to be an essential part of folliculogenesis, although its concentration is not associated with fertilization or implantation rates.     

Follicle-stimulating hormone levels on cycle day 3 are predictive of in vitro fertilization outcome

Cycle day 3 basal levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were measured in 441 patients in 758 consecutive cycles to determine their predictive value for stimulation quality and pregnancy rates in vitro fertilization (IVF). Patients with low basal FSH levels (less than 15 mIU/ml) had higher pregnancy rates per attempt than those with moderate levels (15 to 24.9 mIU/ml), both of which were higher than those with high FSH levels (greater than 25 mIU/ml). Basal LH and E2 values did not improve the predictive value beyond that provided by FSH. Ongoing pregnancy rates per attempt in the low, moderate, and high FSH groups were 17.0%, 9.3%, and 3.6%, respectively (P less than 0.01). The three groups differed significantly in the percentage of patients having two ovaries, the mean number of follicles aspirated per retrieval, the mean number of preovulatory oocytes obtained, and peak E2 values (P less than 0.01). Cycle day 3 FSH levels are predictive of pregnancy outcome and stimulation characteristics in IVF, and may be useful in counseling patients.     

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.     

Urinary reproductive hormone level differences between African American and Caucasian women of reproductive age

OBJECTIVE: To compare urinary levels of reproductive hormones in African American and Caucasian women. DESIGN: Cross-sectional study. SETTING: Ten United States Air Force (USAF) bases. PATIENT(S): African American (n = 33) and Caucasian (n = 65) women of reproductive age from a larger study of USAF women (n = 170). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Urinary endocrine end points: follicular luteinizing hormone (LH), preovulatory LH, level of LH surge peak, early follicular follicle stimulating hormone (FSH), follicular LH:FSH ratio, midluteal FSH, FSH rise before menses, early follicular estrone 3-glucuronide (E(1)3G), midfollicular E(1)3G, periovulatory E(1)3G peak, midluteal E(1)3G, early follicular pregnanediol 3-glucuronide (Pd3G), follicular Pd3G, rate of periovulatory Pd3G increase, E(1)3G:Pd3G on the day of luteal transition, slope of E(1)3G:Pd3G, and midluteal Pd3G. RESULT(S): Relative to Caucasians, African American women had significantly lower follicular phase LH:FSH ratios (mean +/- SD: 0.7 +/- 0.4 vs. 1.0 +/- 0.6), lower follicular phase Pd3G levels (1.0 +/- 0.5 vs. 1.2 +/- 0.8 microg/mg creatinine), and lower rates of periovulatory Pd3G increase (0.5 +/- 0.7 vs. 1.0 +/- 1.2 microg/mg creatinine). CONCLUSION(S): Findings of this analysis should be considered preliminary evidence of racial differences in hormone levels. Future studies are needed to determine whether these differences have clinical significance.     

Fine tuning cycle day 3 hormonal assessment of ovarian reserve improves in vitro fertilization outcome in gonadotropin-releasing hormone antagonist cycles

OBJECTIVE: To identify the cut-off values of the baseline (cycle day 3) levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E(2)) for improving the outcome prediction of GnRH antagonist in vitro fertilization (IVF) cycles and to determine whether the predictive accuracy of these values is affected by the patient's clinical prognosis. DESIGN: Retrospective analysis. SETTING: An IVF clinic in a tertiary medical center.Women undergoing 230 consecutive IVF cycles using a GnRH antagonist protocol. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Outcome of IVF, measured by ovarian response and pregnancy rates. RESULT(S): Lower baseline levels of FSH and E(2), but not LH, correlated with improved ovarian response and pregnancy rates in IVF cycles using a GnRH antagonist. Compared with our currently used criteria, the cut-off values of FSH <10 IU/L and E(2) <56 pg/mL would have significantly improved the IVF outcome in a population of patients with normal prognosis. However, a stricter baseline FSH cut-off value of 8 IU/L would have been required to improve the IVF outcome in a population of patients with a poor prognosis. CONCLUSION(S): The outcome of IVF may be improved by modifying the hormonal starting criteria to take into account individual patient characteristics such as clinical prognosis.     

Exposure to high levels of luteinizing hormone and estradiol in the early follicular phase of gonadotropin-releasing hormone antagonist cycles is associated with a reduced chance of pregnancy

OBJECTIVE: To compare ongoing implantation rates under two different GnRH antagonist protocols. DESIGN: Randomized controlled trial. SETTING: Tertiary referral center. PATIENT(S): One hundred eleven women undergoing ovarian stimulation for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). INTERVENTION(S): Ovarian stimulation with 150 IU recombinant-FSH (rec-FSH) starting on day 2 of the cycle and GnRH antagonist starting either on day 6 of stimulation (fixed group) or when a follicle of > or = 15 mm was present after at least 5 days of stimulation (flexible group). In the flexible group, the rec-FSH dose was increased to 250 IU when the antagonist was initiated. MAIN OUTCOME MEASURE(S): Ongoing implantation and pregnancy rate. RESULT(S): In patients with no follicle of > or = 15 mm present on day 6 of stimulation, a significantly lower ongoing implantation rate was observed if the flexible scheme was applied as compared with the fixed scheme of administration (8.8% vs. 23.9%, respectively). Exposure of the genital tract to LH or E2 from initiation of stimulation to antagonist administration was able to distinguish between pregnant and nonpregnant patients in the population studied. CONCLUSION(S): High exposure of the genital tract to LH and E2 in the early follicular phase is associated with a reduced chance of pregnancy in cycles stimulated with recombinant FSH and GnRH antagonist for IVF/ICSI.     

Effects of anti-Müllerian hormone and follicle stimulating hormone levels on in vitro fertilization pregnancy rate

ObjectivesTo analyze the relationship between in vitro fertilization (IVF) pregnancy rate and basal serum hormone levels before patients begin an IVF course.Materials and methodsIn this retrospective study, we analyzed patients with anti-Müllerian hormone (AMH) data and IVF data from January 2009 to October 2012. Pregnancy rates were calculated by AMH and follicle stimulating hormone quartiles and analyzed using the independent samples t test. Furthermore, patients were divided into three groups by age. The Chi-square test was used to assess the association between the parameters and IVF pregnancy rates.ResultsFrom the 910 IVF treatment courses, 377 (41.4%) clinical pregnancies resulted. The pregnant and nonpregnant groups differed significantly in age and FSH and AMH levels. The pregnancy rate was 53.3% for patients aged <32 years and 22.1% for patients aged >38 years. The pregnancy rate was 53.4% for patients with FSH levels <5.6 mIU/mL and 25.8% for patients with FSH levels >8.9 mIU/mL. The pregnancy rate was 56.8% for patients with AMH levels >4.0 ng/mL and 20.0% for patients with AMH levels <1.1 ng/mL. Furthermore, among patients aged <40 years, AMH and FSH were significantly associated with pregnancy rate. Higher pregnancy rates were found among the groups with higher AMH levels than in groups with lower AMH levels.ConclusionFor patients aged <40 years, basal serum AMH level and FSH level affected the IVF pregnancy rate, and patients with higher AMH levels had better pregnancy rates.     

Prospective, randomized, controlled study of in vitro fertilization-embryo transfer with a single dose of a luteinizing hormone-releasing hormone (LH-RH) antagonist (cetrorelix) or a depot formula of an LH-RH agonist (triptorelin)

OBJECTIVE: To confirm the value of a single dose of 3 mg of cetrorelix in preventing the occurrence of premature LH surges. DESIGN: Multicenter randomized, prospective study. SETTING: Reproductive medicine units. PATIENT(S): Infertile patients undergoing ovarian stimulation for IVF-ET. INTERVENTION(S): A single dose of 3 mg of cetrorelix (Cetrotide; ASTA Medica, Frankfurt, Germany) (115 patients) was administered in the late follicular phase. A depot preparation of triptorelin (Decapeptyl; Ipsen-Biotech, Paris, France) was chosen as a control agent (39 patients). Ovarian stimulation was conducted with hMG (Menogon; Ferring, Kiel, Germany). MAIN OUTCOME MEASURE(S): Premature LH surges (LH level >10 IU/L), progesterone level greater than 1 ng/L, and IVF results. RESULT(S): No LH surge occurred after cetrorelix administration. The patients in the cetrorelix group had a lower number of oocytes and embryos. The percentage of mature oocytes and fertilization rates were similar in both groups, and the pregnancy rates were not statistically different. The length of stimulation, number of hMG ampules administered, and occurrence of the ovarian hyperstimulation syndrome were lower in the cetrorelix group. Tolerance of cetrorelix was excellent. CONCLUSION(S): A cetrorelix single-dose protocol prevented LH surges in all patients studied. It compares favorably to the "long protocol" and could be a protocol of choice in IVF-ET.     

Intercycle variability of day 3 follicle-stimulating hormone levels and its effect on stimulation quality in in vitro fertilization

Prior studies have demonstrated that gonadotropin stimulation quality and pregnancy rates are better in in vitro fertilization (IVF) patients with low basal cycle day 3 follicle-stimulating hormone (FSH) levels. The records of 81 patients who had undergone three or more IVF attempts during a 2-year period were studied to determine the degree and potential impact of intercycle variability in basal FSH concentrations. The mean of the individual standard deviations for all 81 patients was 4.2 +/- 0.4 mIU/mL. However, the patients with a mean basal FSH of less than 15 mIU/mL had a mean deviation of only 2.6 +/- 0.2 mIU/mL, whereas those with a mean basal FSH of greater than or equal to 15 mIU/mL had a mean deviation of 7.3 +/- 0.7 mIU/mL. Intercycle variability in basal FSH values did not predict changes in ovarian response to gonadotropin stimulation and thus may not be used to select an optimal cycle in which to stimulate an individual patient. Furthermore, patients with large intercycle variation responded poorly to gonadotropin stimulation independent of their basal FSH concentration. This information allows more precise counseling of patients regarding their appropriateness for assisted reproduction.     

Do raised serum luteinizing hormone levels during stimulation for in-vitro fertilization predict outcome?

Previous reports associating raised LH concentrations with reduced fertilization and pregnancy rates in women undergoing in-vitro fertilization (IVF) have assumed a Gaussian distribution of LH values with IVF treatment. We have determined the serum LH range during ovarian stimulation for IVF with a single regimen of clomiphene citrate/hMG from 102 consecutive IVF conception cycles. The results show a non-Gaussian distribution of LH values. Application of this LH range to a consecutive series of 596 women undergoing IVF treated with this single regimen showed no difference in pregnancy rates, fertilization rates, median number of oocytes fertilized or retrieved when analysed with respect to serum LH concentrations above the 75th or 95th centile for greater than or equal to 3 days of an IVF treatment cycle. We conclude that follicular-phase LH concentrations do not predict IVF fertilization rates or clinical outcome and are not clinically useful in individual patient management.     

Evaluation of two doses of recombinant luteinizing hormone supplementation in an unselected group of women undergoing follicular stimulation for in vitro fertilization

OBJECTIVE: To evaluate the efficacy of two doses of recombinant (r)LH, 75 IU (recommended) or 37.5 IU, for follicular stimulation and outcomes in a randomized cohort of IVF patients. DESIGN: Randomized, prospective analysis. SETTING: Private hospital incorporating an established IVF center. PATIENT(S): Women undergoing IVF who had a body mass index >18 or <35 and no abnormal karyotype, anovulation, oligomenorrhea, or any known endocrinopathy/illness. INTERVENTION(S): Pituitary desensitization was achieved with triptorelin (0.1 mg SC), and gonadotropin stimulation was performed with either rFSH alone (group A) or in combination with rLH in one of two doses: 37.5 IU (group B) or 75 IU (group C), daily. MAIN OUTCOME MEASURE(S): A range of endocrinologic, embryologic, clinical, and outcome parameters were evaluated. RESULT(S): With rLH supplementation there was a significant increase in the incidence of implantation (9% for rFSH only [group A] vs. 11% and 16% with 37.5 IU rLH and 75.0 IU rLH [groups B and C], respectively) and clinical pregnancy (19% vs. 23% and 31%) (P<.01 and P<.04, respectively), whereas there was no difference in the multiple pregnancy rates. There was a significant (P<.001) increase in the total units of rFSH used in proportion to the amount of rLH supplementation (2,645 U vs. 3,475 U and 3,681 U) and in the level of peripheral E(2) on the day of hCG administration (1,049 pg/mL vs. 1,640 pg/mL and 1,226 pg/mL) (P<.001). There was no significant between difference in mean age, numbers of oocytes recovered, basal and downregulation hormone levels, or the incidence of fertilization in the absence or presence of rLH supplementation, but a higher incidence of grade 1 to 2 embryos was observed when rLH was supplemented. CONCLUSION(S): After pituitary desensitization, there was an increase in the incidence of implantation, clinical pregnancy, and delivery rates in patients stimulated with rFSH supplemented with rLH.     

Stimulation of endogenous surge of luteinizing hormone with gonadotropin-releasing hormone analog after ovarian stimulation for in vitro fertilization

The effect of induction of preovulatory endogenous surge of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) with intranasal administration of GnRH-analog (GnRH-a) in an in vitro fertilization (IVF) program is reported. The use of GnRH-a resulted in a significantly better percentage of replaceable embryos (91% versus 85%). The pregnancy rate was 51% in comparison with 32% in control cycles in which follicular maturation was achieved by human chorionic gonadotropin administration. There was no significant difference in the postoocyte recovery serum progesterone patterns between the two groups. Our results indicate that the induction of endogenous LH and FSH surge with GnRH-a may be successfully employed for final follicular maturation after ovarian suprastimulation without affecting the outcome of IVF adversely. Apart from being a more physiological approach to oocyte maturation, it also has potential economic and clinical advantages.     

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.     

Cessation of gonadotropin-releasing hormone analogue (GnRH-a) upon down-regulation versus conventional long GnRH-a protocol in poor responders undergoing in vitro fertilization.

OBJECTIVE: To determine whether a controlled ovarian hyperstimulation (COH) regimen that involves GnRH agonist (GnRH-a) discontinuation before administration of gonadotropins would benefit poor responders. DESIGN: A prospective, randomized controlled trial. SETTING: Hospital-based IVF Unit. PATIENT(S): Sixty-three patients with previous poor response to COH and/or high basal FSH level (> or =9 mIU/mL) undergoing 78 IVF-ET cycles. INTERVENTION(S): In both groups, administration of GnRH-a was started in the midluteal phase. Whereas in the study group (40 cycles), it ended before administration of gonadotropins, in controls (38 cycles) GnRH-a treatment was continued throughout the follicular phase. MAIN OUTCOME MEASURE(S): Ovarian stimulation patterns and IVF outcome. RESULT(S): A significantly higher cancellation rate was noted in the study group than in the controls (22.5% versus 5%, respectively). The new and control regimens resulted in similar stimulation characteristics and clinical pregnancy rates (11% versus 10.3%, respectively). In 13 patients with a basal FSH level that was not persistently high, the new regimen resulted in a significantly higher number of retrieved oocytes compared with the standard protocol (7.6+/-1.03 versus 4.0+/-0.68, respectively). CONCLUSION(S): Whereas for most low responders, the new COH regimen offers no further advantage, future prospective studies may demonstrate whether it can confer a benefit for a subset of patients with a basal FSH level that is not persistently high.     

Ovarian response and pregnancy outcome related to midfollicular LH levels in down-regulated women undergoing assisted reproduction

OBJECTIVE: To assess ovarian response and pregnancy outcome related to midfollicular luteinizing hormone (LH) levels in normogonadotropic women down-regulated with gonadotropin-releasing hormone-agonist (GnRH-a) (daily and depot) during an assisted reproduction cycle. STUDY DESIGN: In a prospective randomized trial, 50 women were down-regulated with leuprorelin, 0.5 mg/d subcutaneously (group A) and 50 with leuprorelin, 3.75 mg depot (group B), prior to ovarian stimulation with recombinant follicle-stimulating hormone (FSH). Midfollicular serum LH levels < or = 0.5 mIU/mL (subgroups A1 and B1) versus > 0.5 mIU/mL (subgroups A2 and B2) were considered. A comparative analysis was carried out on the clinical effects (duration of stimulation, total FSH dose, number of oocytes retrieved and pregnancy rate). RESULTS: Maximum estradiol levels and pregnancy rates were higher in subgroups A2 and B2, with LH > 0.5 mIU/mL. No differences were observed in the cumulative amount of gonadotropin used, number of oocytes retrieved or fertilization rate. CONCLUSION: When FSH only is used for ovarian stimulation, very low LH serum concentrations in normogonadotropic women profoundly suppressed with GnRH-a, especially if given as a depot, may adversely affect in vitro fertilization outcome.     

Elevated early follicular gonadotropin levels in women with unexplained infertility do not provide evidence for disordered gonadotropin-releasing hormone secretion as assessed by luteinizing hormone pulse characteristics

OBJECTIVE: To determine whether women with rigorously defined unexplained infertility demonstrated altered GnRH secretion, as reflected by serum LH secretion patterns. DESIGN: Prospective observational study. SETTING: National Center for Infertility Research at Michigan. PATIENT(S): Nine women with rigorously defined unexplained infertility and 11 healthy, parous age-matched control women.Gonadotropin-releasing hormone (25 ng/kg) as a bolus injection. MAIN OUTCOME MEASURE(S): Daytime pulse patterns of LH secretion measured every 10 minutes; mean serum concentrations of LH, FSH, E(2), P, PRL, and cortisol; and response to a physiologic dose of GnRH in the early follicular, late follicular, mid-luteal, and late luteal phases of the same menstrual cycle. RESULT(S): Serum LH pulse frequency and pulse amplitude and LH secretion in response to a physiologic bolus of GnRH were not significantly different in unexplained infertility patients at any phase of the cycle. Luteinizing hormone pulse frequency and amplitude, as well as response to GnRH, varied significantly across the cycle. Mean early follicular serum LH and FSH concentrations were significantly higher in unexplained infertility patients than in fertile control subjects (LH: 5.31 +/-.51 vs. 4.03 +/-.33 [mIU/mL +/- SEM]; FSH: 5.81 +/-.63 vs. 3.80 +/-.45) but were not different at any other phase of the cycle. CONCLUSION(S): These data do not support the hypothesis that unexplained infertility is caused by an abnormality in pulsatile GnRH secretion or abnormal pituitary sensitivity to GnRH. However, the results are consistent with a difference in negative feedback from the ovary to the pituitary in unexplained infertility patients that is suggestive of diminished ovarian reserve.     

Metformin treatment of patients with polycystic ovary syndrome undergoing in vitro fertilization improves outcomes and is associated with modulation of the insulin-like growth factors

OBJECTIVE: To determine if metformin therapy improves in vitro fertilization (IVF) outcomes in patients with clomiphene-resistant polycystic ovarian syndrome (PCOS). DESIGN: Retrospective data analysis of selective groups of patients. SETTING: A private IVF unit. PATIENT(S): Forty-six women with clomiphene citrate-resistant PCOS underwent 60 cycles of IVF embryo transfer with intracytoplasmic sperm injection. INTERVENTION(S): In half of the cycles, patients received metformin (1000 to 1500 mg) daily, starting the cycle prior to gonadotropin treatment. MAIN OUTCOME MEASURE(S): Total number of follicles; serum estradiol (E2) on the day of hCG administration and the cycle's E2 maximum; total number of oocytes, mature oocytes, embryos, fertilization, and pregnancy rates; and follicular fluid levels of insulin-like growth factors (IGF-I, IGF-II) and IGF-binding proteins (IGFBP-1, IGFBP-3). RESULT(S): In patients treated with metformin, the total number of follicles on the day of hCG treatment was decreased (23 +/- 1.2 vs. 33 +/- 2.6) with no change in follicles > or = 14 mm in diameter (21 +/- 1.2 vs. 25 +/- 1.7). Metformin treatment did not affect the mean number of oocytes retrieved (22 +/- 1.9 vs. 20.3 +/- 1.5). However, the mean number of mature oocytes (18.4 +/- 1.5 vs. 13 +/- 1.5) and embryos cleaved (12.5 +/- 1.5 vs. 5.9 +/- 0.9) were increased after metformin treatment. Fertilization rates (64% vs. 43%) and clinical pregnancy rates (70% vs.30%) were also increased. Metformin led to modulation of preovulatory of follicular fluid IGF levels with increases of IGF-I (140 +/- 8 vs. 109 +/- 7ng/mL) and decreased of IGFBP-1 (133 +/- 8 vs.153 +/- 9ng/mL). CONCLUSION(S): Metformin use appears to improve IVF outcomes in patients with clomiphene citrate-resistant PCOS.