New insights into the role of LH in early ovarian follicular growth: a possible tool to optimize follicular recruitment.

Evidence shows that LH participates in enhancing transition from the early stage to the antral stage of folliculogenesis. It has been demonstrated that functional LH receptors are expressed, albeit at a very low level and even in smaller follicles, during the phase that was traditionally considered to be gonadotrophin independent, suggesting a role for LH in accelerating the rate of progression of non-growing and primary follicles to the preantral/antral stage. Hypogonadotropic hypogonadism, together with other clinical conditions of pituitary suppression, has been associated with reduced functional ovarian reserve. The reduction in LH serum concentration is associated with a low concentration of anti-Müllerian hormone. This is the case in hypothalamic amenorrhoea, pregnancy, long-term GnRH-analogue therapy and hormonal contraception. The effect seems to be reversible, such that after pregnancy and after discontinuation of drugs, the functional ovarian reserve returns to the baseline level. Evidence suggests that women with similar primordial follicle reserves could present with different numbers of antral follicles, and that gonadotrophins may play a fundamental role in permitting a normal rate of progression of follicles through non-cyclic folliculogenesis. The precise role of gonadotrophins in early folliculogenesis, as well as their use to modify the functional ovarian reserve, must be investigated.

Chronic endometritis in recurrent implantation failure: Use of prednisone and IVF outcome.

In recurrent implantation failure patients (RIF), the main criteria for diagnosis of chronic endometritis, is the presence of plasma cells CD138+ in endometrial biopsy. The aim of the present study was to evaluate if treatment with prednisone, in patients with RIF and chronic endometritis, improve IVF outcome. A retrospective study was performed between 2019 and 2020. A total of 27 patients with RIF and an endometrial biopsy positive for CD56+ cells were enrolled. The treatment with prednisone 10 mg per day is began together with controlled ovarian stimulation (COS). Among endometrial biopsies, 13 (48.14%) were positive also for CD138 cells, and an antibiotic treatment was added. In all patients, after therapy, in the subsequent IVF cycle, the clinical pregnancy rate was 25.9% and the live birth rate was 22.2%. Analysing pregnancies according to the percentage of CD 56 cells on endometrial biopsy, the live birth rate in the subgroup of patients with marked endometritis (defined by the presence of >10% CD56+cells) was 29.41%, while in the subgroup with mild endometritis (CD 56 >5% and <10%) was 10%. In the subgroup with mild endometritis with CD 138 positive the live birth was 25%, while in patients with CD 138 negative no live birth were observed. In patients with RIF the count of at least two cell types (CD 138 and CD 56 cells) on endometrial biopsies is advisable. Our study suggests a benefit of prednisone and antibiotic treatment on live birth rate in a subsequent IVF cycle.

Modulation of gonadotrophin induced steroidogenic enzymes in granulosa cells by d-chiroinositol.

BACKGROUND: d-chiroinositol (DCI) is a inositolphosphoglycan (IPG) involved in several cellular functions that control the glucose metabolism. DCI functions as second messenger in the insulin signaling pathway and it is considered an insulin sensitizer since deficiency in tissue availability of DCI were shown to cause insulin resistance (IR). Polycystic ovary syndrome (PCOS) is a pathological condition that is often accompanied with insulin resistance. DCI can positively affects several aspect of PCOS etiology decreasing the total and free testosterone, lowering blood pressure, improving the glucose metabolism and increasing the ovulation frequency. The purpose of this study was to evaluate the effects of DCI and insulin combined with gonadotrophins namely follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on key steroidogenic enzymes genes regulation, cytochrome P450 family 19 subfamily A member 1 (CYP19A1) and cytochrome P450 side-chain cleavage (P450scc) in primary cultures of human granulosa cells (hGCs). We also investigated whether DCI, being an insulin-sensitizer would be able to counteract the expected stimulator activity of insulin on human granulosa cells (hGCs). METHODS: The study was conducted on primary cultures of hGCs. Gene expression was evaluated by RT-qPCR method. Statistical analysis was performed applying student t-test, as appropriate (P < 0.05) set for statistical significance. RESULTS: DCI is able to reduce the gene expression of CYP19A1, P450scc and insulin-like growth factor 1 receptor (IGF-1R) in dose-response manner. The presence of DCI impaired the increased expression of steroidogenic enzyme genes generated by the insulin treatment in gonadotrophin-stimulated hGCs. CONCLUSIONS: Insulin acts as co-gonadotrophin increasing the expression of steroidogenic enzymes genes in gonadotrophin-stimulated granulosa cells. DCI is an insulin-sensitizer that counteracts this action by reducing the expression of the genes CYP19A1, P450scc and IGF-1R. The ability of DCI to modulate in vitro ovarian activity of insulin could in part explain its beneficial effect when used as treatment for conditions associated to insulin resistance.

The anti-Müllerian hormone (AMH) acts as a gatekeeper of ovarian steroidogenesis inhibiting the granulosa cell response to both FSH and LH.

PURPOSE: Anti Müllerian Hormone (AMH) has a negative and inhibitory role in many functions of human granulosa-lutein cells (hGCs) including notoriously the reduction of the aromatase CYP19A1 expression induced by follicle-stimulating hormone (FSH). No data have been provided on the possible role of AMH in modulating the response to luteinizing hormone (LH) (alone or combined with FSH) as well as its effect on other enzymes involved in steroidogenesis including aromatase P450scc. The aim of this study was to investigate the role of AMH as regulator of the basal and stimulated steroids production by hGCs. METHODS: Primary culture of hGCs were incubated with hormones AMH, LH, and FSH, alone or in combination. The CYP19A1 and P450scc messenger RNA (mRNA) expression, normalized by housekeeping ribosomal protein S7 (RpS7) gene, was evaluated by reverse transcriptase quantitative PCR (RT-qPCR). Each reaction was repeated in triplicate. Negative controls using corresponding amount of vehicle control for each hormone treatment were performed. RESULT: AMH did not modulate the basal mRNA expression of both aromatase genes at any of the concentrations tested. Meanwhile, the strong mRNA induction of CYP19A1 and P450scc generated by a 24-h gonadotropin treatment (alone and combined) was suppressed by 20 ng/ml AMH added to culture medium. CONCLUSIONS: These findings contribute in clarifying the relationship between hormones regulating the early phase of steroidogenesis confirming that AMH is playing a suppressive role on CYP19A1 expression stimulated by gonadotropin in hGCs. Furthermore, a similar inhibitory effect for AMH was observed on P450scc gene expression when activated by gonadotropin treatment.

Live birth rates in the different combinations of the Bologna criteria poor ovarian responders: a validation study.

PURPOSE: to compare the baseline characteristics and chance of live birth in the different categories of poor responders identified by the combinations of the Bologna criteria and establish whether these groups comprise a homogenous population. METHODS: database containing clinical and laboratory information on IVF treatment cycles carried out at the Mother-Infant Department of the University Hospital of Modena between year 2007 and 2011 was analysed. This data was collected prospectively and recorded in the registered database of the fertility centre. Eight hundred and thirty women fulfilled the inclusion/ exclusion criteria of the study and 210 women fulfilled the Bologna criteria definition for poor ovarian response (POR). Five categories of poor responders were identified by different combinations of the Bologna criteria. RESULTS: There were no significant differences in female age, AFC, AMH, cycle cancellation rate and number of retrieved oocytes between the five groups. The live birth rate ranged between 5.5 and 7.4 % and was not statistically different in the five different categories of women defined as poor responders according to the Bologna criteria. CONCLUSION: The study demonstrates that the different groups of poor responders based on the Bologna criteria have similar IVF outcomes. This information validates the Bologna criteria definition as women having a uniform poor prognosis and also demonstrates that the Bologna criteria poor responders in the various subgroups represent a homogenous population with similar pre-clinical and clinical outcomes.

Cervical nitric oxide metabolite levels and clinical variables as predictive factors of high-grade cervical intraepithelial neoplasia.

PURPOSE: To create a prediction model of high-grade cervical intraepithelial neoplasia (CIN) based on clinical variables and the cervical nitric oxide metabolite (NOx) levels of study participants. METHODS: This comparative study included 694 women undergoing colposcopy due to abnormal pap smear results. On the basis of the cervical biopsy results, the women were divided into the ≤ CIN 1 or CIN 2-3 group. The two groups were compared in terms of cervical NOx levels and clinical variables. Univariate, multivariate, and receiver-operating characteristic curve analysis were performed. RESULTS: Multivariate analysis showed that CIN 2-3 associated with more than two cervical biopsies [odds ratio (OR) = 5.16], high-grade squamous intraepithelial lesion cytology (OR = 16.19), condom non-use (OR = 4.28), cervical NOx levels ≤ 99.9 µmol/L (OR = 16.62), more than four lifetime male sexual partners (OR = 10.56), and age at first coitus of ≤ 15 years old (OR = 3.54). This combined model had a sensitivity of 86.49 %, a specificity of 90.74 %, a positive predictive value of 64.0 %, and a negative predictive value of 97.2 %. CONCLUSIONS: In the present sample, high-grade CIN associated with decreased cervical NOx levels. Thus, along with some clinical variables, cervical NOx levels may be an additional marker of cervical dysplasia.

Individualization of the FSH starting dose in IVF/ICSI cycles using the antral follicle count.

BACKGROUND: The FSH starting dose is usually chosen according to women's age, anamnesis, clinical criteria and markers of ovarian reserve. Currently used markers include antral follicle count (AFC), which is considered to have a very high performance in predicting ovarian response to FSH. The objective of the present study to elaborate a nomogram based on AFC for the calculation of the appropriate FSH starting dose in IVF cycles. METHODS: This is a retrospective study performed at the Mother-Infant Department of Modena University Hospital. IVF patients (n=505) were subjected to blood sampling and transvaginal ultrasound for measurement of serum day3 FSH, estradiol and AFC. The variables predictive of the number of retrieved oocytes were assessed by backwards stepwise multiple regression. The variables reaching the statistical significance were then used in the calculation for the final predictive model. RESULTS: A model based on age, AFC and FSH was able to accurately predict the ovarian sensitivity and accounted for 30% of the variability of ovarian response to FSH. An FSH dosage nomogram was constructed and overall it predicts a starting dose lower than 225 IU in 50.2% and 18.1% of patients younger and older than 35 years, respectively. CONCLUSIONS: The daily FSH dose may be calculated on the basis of age and two markers of ovarian reserve, namely AFC and FSH, with the last two variables being the most significant predictors. The nomogram seems easily applicable during the daily clinical practice.

Nitric Oxide concentration in endometrial washing throughout the menstrual cycle.

PURPOSE: Nitric oxide (NO) intrauterine production has been shown to have an important role in the reproductive system in females. The objective of the present study was to evaluate NO concentration in endometrial washing throughout the menstrual cycle. METHODS: Observational study at Institute of Obstetrics and Gynecology, Mother-Infant Department, University Hospital. The study included 40 healthy fertile women, aged 21-40, with regular menstrual cycle, undergoing endometrial washing by hydrosonography for the assessment of NO concentration. RESULTS: Nitric oxide concentration in endometrial washing were low in early to mid proliferative phase (4.73 ± 1.57 mcM/L), but significantly higher (p < 0.05) in late proliferative phase (7.30 ± 3.37 mcM/L) early secretory phase (8.05 ± 1.97 mcM/L) and late secretory phase (8.69 ± 4.12 mcM/L) of menstrual cycle. CONCLUSIONS: Endometrial washing by hydrosonography is a simple, minimally invasive, and effective tool to use in the evaluation of cyclical NO intrauterine production. Nitric oxide concentrations increased during the late proliferative and secretory phase of menstrual cycle.

Nitric oxide metabolite levels and assessment of cervical length in the prediction of preterm delivery among women undergoing symptomatic preterm labor.

OBJECTIVE: To evaluate the diagnostic accuracy of measuring cervical length (CL) in combination with cervical and plasma nitric oxide metabolite (NOx) levels to identify women undergoing preterm labor (PTL) who will deliver preterm. METHODS: A hospital-based prospective cohort study of 730 women undergoing spontaneous PTL between 24 and 33 weeks+6 days of pregnancy was conducted. Measurement of cervical and plasma NOx levels and ultrasonographic assessment of CL were performed to find the best model to predict preterm delivery (PTD). Optimal cut-off values were calculated by receiver operating characteristic (ROC) curve analysis. Logistic regression analysis and rank correlation tests were also performed. RESULTS: CL of 15 mm or less, cervical NOx levels greater than 87.6 µmol/L, and plasma NOx levels greater than 123 µmol/L (P<0.0001) were the only factors significantly associated with PTD within 7 days of sampling. This combined model provided high diagnostic accuracy (sensitivity 80.0%; specificity 99.2%). Both cervical and plasma NOx levels were negatively correlated with CL (r=-0.453, P<0.0001 and r=-0.362, P<0.0001, respectively). CONCLUSION: Combined measurement of CL and levels of cervical and plasma NOx could help identify women undergoing symptomatic PTL who are at increased risk of PTD.

Periodontal disease and nitric oxide levels in low risk women with preterm labor.

OBJECTIVES: The aims of the study were to evaluate the possible association between periodontal disease (PD) and preterm labor (PTL), to assess whether the presence of periodontal disease in women with PTL increases the risk of preterm birth (PTB), and to evaluate the role of nitric oxide (NO) in this possible association. STUDY DESIGN: This study included 820 nulligravid women with low risk socioeconomic status: 400 cases with PTL and 420 controls with normal pregnancy, between 25 and 33 weeks+6 days of weeks' gestation. At enrollment, periodontal examination and detection of plasma, gingival and cervical NO levels were performed. We compared the periodontal status of the two groups; we detected the presence of PD and compared NO levels. We then followed the outcome of women with PTL and compared obstetric status and PTB rate between patients with and without PD. RESULTS: Logistic regression analysis revealed a strong association between PD and PTL (adjusted odds ratio: 2.83, 95% confidence interval (CI) 1.86-4.23; P<0.0001). Non parametric Mann-Whitney U-test demonstrated significant differences in gingival and cervical NO levels between women with PTL and controls (respectively, median 85.1 µmol/L, interquartile range (i.r.) 51.2-177 vs median 50.5 µmol/L, i.r. 34.5-109.65, P<0.0001; and median 102 µmol/L, i.r. 53.05-182.7 vs median 38.9 µmol/L, i.r. 32.87-46.1, P<0.0001). The ability of mean-gingival NO levels to predict PTL was examined by ROC curve analysis: the area under the curve was 0.817 (95% CI 0.774-0.854; P<0.0001). The cut-off level for the greatest sensitivity and specificity for mean-gingival NO levels was 116.04 µmol/L (sensitivity 0.57, specificity 0.94). Positive and negative predictive values were, respectively, 90.65% and 69.73%. Among women with PTL, the risk of PTB increased in women with PD (adjusted relative risk: 3.85, 95% CI 2.11-6.06; P<0.0001). CONCLUSIONS: In this tested population, PTL is associated with PD. The presence of PD in women with PTL increases the risk of premature delivery. NO may be a new marker to explain this association.

Hormonal and ultrasound markers of ovarian function in a woman with a balanced 1;11 translocation.

OBJECTIVE: To present a case of a poor responder woman with a rare balanced autosomal translocation. DESIGN: Case report. SETTING: Infertility center in a university teaching hospital. PATIENT(S): A 34-year-old white woman with primary infertility. INTERVENTION(S): Laboratory and ultrasound evaluation, karyotype analysis, ovarian stimulation with gonadotropins. MAIN OUTCOME MEASURE(S): Markers of ovarian reserve and ovarian response to gonadotropin stimulation. RESULT(S): The patient was a carrier of a balanced translocation (1;11) (q23;p11.2). The hormone ovarian reserve markers (FSH, anti-Mullerian hormone, inhibin B) were within the normal range. The antral follicle count (AFC) was measured twice and only in one occasion did it reach the lower limit of the normal range. Furthermore, the patient had regular menstrual cycles. However, ovarian response to the administration of a maximal dose FSH was extremely poor. CONCLUSION(S): Patients with balanced autosomal translocations should be counseled regarding their increased risk for poor response even if markers of ovarian reserve are in the range of normality.

Age-specific nomogram for the decline in antral follicle count throughout the reproductive period.

OBJECTIVE: To investigate the relationship between antral follicle count (AFC) and chronological age and to establish normal values for AFC in women with regular menstrual cycles. DESIGN: Cross-sectional study. SETTING: University hospital. PATIENT(S): Four hundred fifteen premenopausal women were recruited for the study. Data from 362 patients were available for the statistical analysis. INTERVENTION(S): AFC was measured by transvaginal ultrasound examination. MAIN OUTCOME MEASURE(S): Estimating the relationship between AFC and age and developing the AFC nomogram. RESULT(S): The analysis showed a linear decline in AFC with age; for every year increase in age, the median AFC decreases by 0.4. The AFC corresponding to the 5th, 25th, 50th, 75th, and 95th centiles for each age have been calculated. CONCLUSION(S): A linear relationship of AFC to age was found. For the first time, a nomogram reporting normal and interquartile values for AFC, age by age, throughout the reproductive period has been provided. Until now, the interpretation of the measurement was mainly based on the individual experience of the operator, because no normative data were present. Therefore, the establishment of a nomogram of AFC values is the first step to counsel patients on a scientific basis.

Adnexal Torsion during Pregnancy after Oocyte In Vitro Maturation and Intracytoplasmic Sperm Injection Cycle.

We report a case of right adnexal torsion during pregnancy after an oocyte in vitro maturation and intracitoplasmic sperm injection cycle in patient with polycystic ovary syndrome. A 31-year-old woman with a typical clinical disorder of polycystic ovarian syndrome was included in an oocyte in vitro maturation program. Right adnexal torsion occurred two days after embryo transfer, and laparoscopy detorsion was successfully performed with preservation of adnexa. The patient had a full-term pregnancy and delivered a healthy infant at 40 weeks of gestation. To our knowledge this is the first report of adnexal torsion after an oocyte in vitro maturation and intracitoplasmic sperm injection program.

Hemoperitoneum in pregnancy from a ruptured varix of broad ligament.

We present a case of a 31-year-old woman, gravida 4 para 1, pregnant at 33 + 2 weeks of gestational age with acute abdomen due to hemoperitoneum. Hemoperitoneum was suspected for non-specific symptoms such as acute abdominal pain, vomit, cardiotocography alterations and maternal acute anaemia. An emergency caesarean section was performed; 3 L of blood was present in abdomen. Careful exploration of the uterus, placenta, abdominal organs and vessels was negative; only a bleeding from a rupture in a varix of the left broad ligament was observed. Hemoperitoneum due to a ruptured uterine varix in pregnancy is a rare condition. The solution to prevent the development of maternal hypovolemic shock is an immediate surgical intervention. A good foetal prognosis principally depends from gestational age and from good hemodynamic maternal conditions.

Embryo quality and implantation rate in two different culture media: ISM1 versus Universal IVF Medium.

OBJECTIVE: To compare the outcome of two different culture media marketed by the MediCult AS Company (Jyllinge, Denmark)-Universal IVF Medium and ISM1 Medium culture-which, in addition to glucose, pyruvate, and energy-providing components, also contain amino acids, nucleotides, vitamins, and cholesterol. DESIGN: Laboratory and retrospective clinical study. SETTING: University teaching hospital. PATIENT(S): A total of 726 patients, undergoing IVF-intracytoplasmic sperm injection procedure, comparable in mean age range, oocyte retrieval, and infertility indication, were included in the study. Laboratory quality and standard procedures were maintained unaffected. INTERVENTION(S): Oocyte retrieval, different embryo culture media. MAIN OUTCOME MEASURE(S): Embryo quality, ongoing pregnancy, and implantation rate. RESULT(S): The frequency of good-quality embryos (79% vs. 74%) and the percentages of ongoing pregnancy (27.5% vs. 18%) and implantation rate (15% vs. 10%) were significantly higher in the group treated with ISM1 Medium rather than Universal IVF Medium. CONCLUSION(S): ISM1 Medium culture seems to improve the performance of embryonic growth and development, as well as increasing the percentage of pregnancy.

Seminal plasma total antioxidant capacity and semen parameters in patients with varicocele.

Total antioxidant capacity (TAC) was evaluated in the seminal plasma of infertile patients with varicocele in relation to their semen parameters. The study recruited 60 patients affected by varicocele and 10 fertile non-varicocele subjects as controls. Controls had normal semen parameters and proven fertility. On the basis of semen parameters, patients with varicocele were grouped into normozoospermic (n = 12), asthenozoospermic (n = 8), oligoasthenozoospermic (n = 40). The group with oligosthenozoospermia was divided into mild (<20 x 10(6)/ml; > or =15 x 10(6)/ml), moderate (<15 x 10(6)/ml; > or =5 x 10(6)/ml), and severe (<5 x 10(6)/ml), based on sperm count. Antioxidant activity was measured in seminal plasma and peripheral blood using the free oxygen radicals defence test. No significant differences were observed in peripheral blood TAC concentrations between controls and groups. In patients with varicocele and moderate oligoasthenozoospermia or severe oligoasthenozoospermia, seminal plasma TAC concentrations were significantly lower (P < 0.05) than in controls and normozoospermic patients with varicocele. Moreover, in patients with severe oligosthenozoospermia, seminal plasma TAC concentrations were also significantly lower (P < 0.05) than in asthenozoozpermic patients with varicocele. In all subjects, concentrations of TAC showed a positive correlation with sperm concentration (r = 0.93, P < 0.05) and motility (r = 0.92, P < 0.05).

Human ovarian tissue cryopreservation: effect of sucrose concentration on morphological features after thawing.

Recent improvements in techniques in clinical assisted reproduction have led to an increased interest in the cryopreservation of human ovarian tissue as a way of preserving fertility and ovarian steroidogenic activity in young cancer patients. Acceptable follicular survival in frozen-thawed human ovarian tissue has generally been reported. Since a 0.3 mol/l sucrose concentration in cryopreservation solutions evidently increases human oocyte survival after cryopreservation, the aim of this study was to observe the effect of sucrose concentrations of 0.2 mol/l and 0.3 mol/l on human ovarian tissue survival after thawing. Ovarian cortical slices from 10 patients, 22-36 years of age, were cryopreserved slowly using 0.2 mol/l or 0.3 mol/l sucrose with 1,2-propanediol (1.5 mol/l) as the cryoprotectants. Light and electron microscopy were used for the histological analyses. Results showed that both treatments produced an increase in damaged cells; however, the use of 0.3 mol/l sucrose showed a smaller percentage of damaged germ cells than 0.2 mol/l sucrose, and therefore was less detrimental to the thawed ovarian tissue. However as the damage occurred principally in the stroma and follicular cells rather than in the oocytes, the suitability of these cryopreservation protocols must be further evaluated prior to considering the use of stored ovarian cortex for autografting after thawing.

Does plasma insulin level affect ovarian response to exogenous administration of follicle-stimulating hormone in women without polycystic ovary syndrome?

BACKGROUND: Raised insulin levels have been shown to contribute to ovarian overproduction of androgens. Hyperinsulinemia, usually associated with polycystic ovary syndrome (PCOS), brings about greater ovarian endocrine and morphological responses to ovulation induced by follicle-stimulating hormone (FSH). This indicates that elevated levels of insulin play a role in the endocrine and paracrine control of the ovaries. OBJECTIVE: The aim of the present study was to investigate whether basal insulin levels influence ovarian response to FSH in healthy women (non-PCOS) undergoing assisted reproduction by in vitro fertilization-embryo transfer (IVF-ET). METHODS: The study included 36 consecutive women, 27-45 years old, undergoing IVF-ET for tubal-factor or male-factor infertility. Serum insulin levels were determined on the day of administration of gonadotropin-releasing hormone analog (GnRHa) and on the first day of FSH administration. RESULTS: Mean insulin levels were 6 +/- 3 and 7 +/- 3 microU/ml on the day of GnRHa and FSH administration, respectively. No correlations were found between basal insulin level, days of treatment, total FSH dose, estradiol level and the number of oocytes retrieved. CONCLUSIONS: The results of the present study show that normal levels of insulin do not seem to influence ovarian response to FSH in non-PCOS women. In all patients included in our study, serum insulin levels did not correlate with IVF stimulation data (days of stimulation, total FSH dose) nor with IVF-ET outcome. Thus the study demonstrates that, in patients who are not insulin-resistant, insulin does not correlate with ovarian response to FSH administration.

Comparison of a gonadotropin-releasing hormone (GnRH) antagonist and GnRH agonist flare-up regimen in poor responders undergoing ovarian stimulation.

OBJECTIVE: To compare the efficacy of flare-up and GnRH-antagonist treatment in poor-responder patients. DESIGN: Randomized prospective study. SETTING: Assisted reproduction center. PATIENT(S): Fifty-five poor-responder patients undergoing intracytoplasmic sperm injection (ICSI). INTERVENTION(S): Thirty patients received GnRH agonist on the 1st day of menstruation, followed by exogenous gonadotropins from the 2nd day. Twenty-five patients received exogenous gonadotropins starting on the second day of menstruation, followed by GnRH antagonist when the leading follicle reached 14 mm in diameter. MAIN OUTCOME MEASURE(S): The total dose of FSH administered during the ovarian stimulation, as well as the number of mature oocytes retrieved, embryo quality, fertilization, implantation, and pregnancy rates were evaluated. RESULT(S): The number of ampules and units of FSH administered were significantly less in the flare-up than in the antagonistic group. The numbers of mature oocytes retrieved and of top-quality embryos transferred were significantly greater in the flare-up than in the GnRH-antagonist group. The fertilization rate (84% vs. 63%) was significantly higher in the flare-up than in the GnRH-antagonist group. The implantation and pregnancy rate were similar in the two groups. CONCLUSION(S): The flare-up protocol appears to be more effective than the GnRH-antagonist protocol in terms of mature oocytes retrieved, fertilization rate, and top-quality embryos transferred in poor-responder patients.