Is assisted hatching beneficial in patients with recurrent implantation failures?

PURPOSE: To assess the possible role of assisted hatching in patients with recurrent implantation failure during IVF cycles. DESIGN: Prospective randomized study. SETTING: IVF unit of an academic medical center. PATIENTS: Women who underwent IVF after at least three failed IVF-ET attempts. INTERVENTIONS: Patients were prospectively randomized to undergo assisted hatching of their embryos prior to their replacement by mechanical partial zona dissection. RESULTS: The study (assisted hatching) and control groups included 104 and 103 patients, respectively. There were no significant between-group differences in patient age, cause of infertility, mean number of previous IVF trials, number of oocytes retrieved, fertilization rate, or number of embryos transferred. No difference in pregnancy rate was noted on comparison of the whole study group, to the whole control group (21% and 27%, respectively). However, when the results were re-analyzed by age groups, assisted hatching was found to be harmful in the youngest group (< 34 years), significantly decreasing pregnancy rates (15% vs 35%, p < 0.05). CONCLUSION: Repeated implantation failure alone is not an indication for assisted hatching. Although assisted hatching appears to be effective in a selected group of older patients, in younger patients it may further hamper implantation and should be avoided.

Inclusion of standard and low-dose gonadotropin releasing hormone-analog (short protocol) in controlled ovarian hyperstimulation regimens in normogonadotropic patients aged 40-48 years who are undergoing in vitro fertilization.

We aimed to compare the efficiency of three controlled ovarian hyperstimulation protocols in achieving superovulation in normogonadotropic patients aged 40 years or more, who were undergoing in vitro fertilization (IVF) treatment. This was a prospective randomized clinical study, carried out in the Infertility and IVF Unit of an academic tertiary hospital. A total of 219 normogonadotropic patients (serum follicular stimulating hormone level < 15 mIU/ml) aged 40-48 years, with regular menstrual cycles, were randomly allocated to one of three short follicular protocols: menotropins only (group A), menotropins plus a mini-dose of gonadotropin releasing hormone (GnRH)-analog (600 microg/ day) (group B), or menotropins plus a standard dose (900 microg/day) of a GnRH-analog (group C). Those cycles that reached the stage of oocyte retrieval (67, 70 and 71 cycles, respectively) were analyzed. The mean daily dose of menotropins needed for ovarian stimulation was higher when GnRH-analog was used (groups B and C) (p < 0.02; ANOVA), although there was no significant difference in the time of human chorionic gonadotropin injection (average: cycle day 11). Peak estradiol levels (p < 0.02), number of oocytes retrieved (3.9, 5.4 and 5.5 oocytes/cycle, respectively, p < 0.02) and number of embryos transferred (1.6, 1.8 and 2.1 embryos/cycle, respectively, p < 0.05) were higher when GnRH-analog was included in the controlled ovarian hyperstimulation protocol. The IVF treatment resulted in 19 pregnancies (9.1% implantation rate), with a similar distribution among all three groups (11.9%, 8.6% and 7.0%). However, a higher miscarriage rate was noted in the menotropins-only group (67.5% vs. 33.3% and 40.0% of pregnancies). No differences were observed in any of the aforementioned variables between the mini-dose and standard dose GnRH-analog groups (groups B and C). In conclusion, controlled ovarian hyperstimulation before IVF treatment in normogonadotropic patients aged 40 years or more is more effective when a GnRH-analog (short protocol) is included in the treatment regimen. In this selected group of patients, reducing the daily dose of GnRH-analog does not improve the treatment results.

Ultrasound-guided testicular sperm aspiration in azoospermic patients: a new sperm retrieval method for intracytoplasmic sperm injection.

PURPOSE: We investigated the technique of ultrasound-guided testicular sperm aspiration (USTSA) and compared it with "blind" testicular sperm aspiration (TSA) in patients with nonobstructive azoospermia. METHODS: Thirty-nine consecutive azoospermic men underwent TSA, 16 under sonographic guidance (USTSA group) and 23 with no imaging guidance (TSA group). Clinical and hormonal evaluation and sonography of the scrotum and testes were performed 1-2 days before the procedure. The aspiration was done using short-term general anesthesia. Follow-up consisted of sonographic reexamination of the scrotum and testes immediately and 1 month after the procedure. RESULTS: Intraoperative sonography with power Doppler imaging enabled good visualization of the testicular parenchyma, easy sampling, and avoidance of prominent vessels. Sufficient material was retrieved in 15 USTSA patients (94%) and 19 TSA patients (83%). No patients needed more than 4 hours' ambulatory hospitalization after the procedure. In the remaining 5 patients, aspiration failed to yield sperm, so open biopsy was performed. In those patients, postaspiration surgical exploration revealed subtunical bleeding in 3 patients after TSA but none after USTSA. Late minor complications occurred in 2 patients (13%) in the USTSA group and 7 (30%) in the TSA group. No difference was found between the 2 groups in pregnancy rate in the patients' female partners. CONCLUSIONS: USTSA is a safe and accurate method for sperm retrieval in azoospermic patients.

Focal testicular lesion after sperm extraction or aspiration: sonographic appearance simulating testicular tumor.

OBJECTIVE. We describe the sonographic features of focal intratesticular lesions seen in men who underwent sperm retrieval procedures. CONCLUSION. Although many urologists believe that solid intratesticular masses are malignant until proven otherwise, a growing number of benign focal testicular lesions have been described. Awareness of the cause and sonographic appearance of focal abnormalities in men who have undergone testicular aspiration or extraction should help radiologists suggest the correct diagnosis and advise a conservative approach on the basis of close surveillance by serial physical, laboratory, and imaging studies.

Gonadotropin stimulation following GnRH-a priming for poor responders in in vitro fertilization-embryo transfer programs.

The effect of gonadotropin-releasing hormone agonist (GnRH-a) administration before gonadotropin superovulation on the stimulation characteristics of poor responder patients was assessed in an in vitro fertilization (IVF) program. Thirty consecutive patients who had exhibited low ovarian response (fewer than four retrieved oocytes) in at least two previous IVF cycles (control cycles, n = 60), were eligible for the study. GnRH-a (nafarelin) was administered daily for 7-10 days from the mid-luteal phase of the previous cycle until the first day of menstruation. Menotropin treatment was commenced on cycle day 3 (with no additional GnRH-a) (study cycles, n = 39). A significantly higher number of oocytes was retrieved (p < 0.0002) and a higher number of embryos transferred (p < 0.003) in the study cycles than in the control cycles. No cases of premature luteinizing hormone surge were recorded. Pregnancy rates per embryo transfer and per cycle were 10.4% and 7.7% for the study cycles and 2.8% and 1.6% for the control cycles, respectively. GnRH-a, administered prior to gonadotropin treatment, should be an additional option of ovulation induction protocol for poor responders in IVF programs.

Is diagnostic testicular fine needle aspiration necessary in azoospermic men before sperm aspiration/extraction for intracytoplasmic sperm injection cycles?

PURPOSE: To determine whether diagnostic testicular fine needle aspiration (TEFNA) sampling needs to be performed in azoospermic men prior to obtaining testicular sperm cells for IVF-ICSI procedures. METHODS: Ten azoospermic patients underwent TEFNA in 1993-1996. During 1997, all patients underwent testicular sperm aspiration (TESA) and/or testicular sperm extraction (TESE) to retrieve spermatozoa for IVF-ICSI cycles. The results of the two procedures performed in two separate hospitals were compared. RESULTS: Diagnostic TEFNA revealed spermatozoa in five patients; identical results in four were found during IVF-ICSI cycles. In three patients, only Sertoli cells were found on TEFNA, in two of them TESA/TESE showed identical results, and in one, two spermatozoa were detected by Cyto-SEM. In the remaining two patients, spermatids or spermatocytes were found on both procedures. CONCLUSIONS: There was a very good correlation between the diagnostic and therapeutic procedures. We suggest that in azoospermic patients, diagnostic TEFNA is valuable in order to avoid unnecessary controlled ovarian hyperstimulation in the female partner for IVF. In patients in whom spermatozoa are detected, cryopreservation may be performed for later IVF-ICSI cycles.

Fracture of the clavicle in the newborn following normal labor and delivery.

OBJECTIVE: Earlier works have associated neonatal clavicular fracture (0.2-3.5% of all deliveries) with a range of procedural, fetal and maternal risk factors; more recent studies, however, have failed to firmly identify any one or a combination of them. In the present work we sought to determine possible ante/intra-partum risk factors for this condition. STUDY DESIGN: Using a retrospective case-controlled approach, we examined a series of maternal, fetal and pregnancy or delivery-related variables in 87 cases (out of 403) of fractured clavicle of the newborn diagnosed in our department from 1986 to 1994. All infants were delivered vaginally (in the occipito-anterior position) at term by a specialist obstetrician and underwent peripartum sonographic fetal weight estimation. All variables were compared with those of an equal number of infants born immediately before or after each affected infant and delivered by the same obstetrical team. RESULTS: Fractured clavicles were found in 1.65% of the total number of deliveries during the study period. Neonatal clavicular fracture was significantly and directly related to the duration of the second stage of labor, peripartum sonographic fetal weight estimation, and neonatal length, and inversely related to maternal height; nevertheless, all values in both the study and control groups were within normal range. Logistic regression analysis showed that these antenatal variables significantly affect the chances of clavicular fracture, but due to the high false-positive rate they cannot serve clinically as a comprehensive antenatal prediction index. CONCLUSIONS: The majority of clavicular fractures occur in normal newborns following normal labor and delivery. The risk factors we identified statistically do not offer a method for clinical prenatal prediction. This work provides statistical evidence of the nature of this complication of early newborn life.

Doppler parameters of uterine and ovarian stromal blood flow in women with polycystic ovary syndrome and normally ovulating women undergoing controlled ovarian stimulation.

OBJECTIVE: To test the hypothesis that the increased ovarian sensitivity to gonadotropins observed in women with polycystic ovary syndrome (PCOS) may be due to changes in ovarian stromal blood flow in these patients. DESIGN: Uterine and ovarian stromal arterial blood flow (with transvaginal color Doppler ultrasound) were measured in ten women with PCOS and 12 normo-ovulatory women (control group), undergoing gonadotropin stimulation before in vitro fertilization. METHODS: A careful ovarian stimulation strategy was adopted for the study group in order to avoid ovarian hyperstimulation syndrome and achieve an ovarian response which was comparable to that of the control group. Resistance and pulsatility indices (RI and PI) of the uterine and ovarian stromal arteries were calculated before the onset of gonadotropin treatment, on cycle day 5 (after commencing treatment), day of human chorionic gonadotropin injection, day of ovum pick-up as well as on the day of embryo transfer, and 7 and 12 days later. RESULTS: No significant differences were found in RI and PI between the study and control groups throughout the treatment cycle. CONCLUSIONS: It seems that polycystic ovaries do not bear an inherent disturbance in blood flow dynamics of the uterine and ovarian arteries, as measured by color Doppler, which would explain the increased sensitivity of polycystic ovaries to stimulation with gonadotropins.

Effect of parental age on fertilization and pregnancy characteristics in couples treated by intracytoplasmic sperm injection.

The purpose of this study was to investigate any influence of maternal and/or paternal age on gamete characteristics and pregnancy outcomes in intracytoplasmic sperm injection (ICSI) cycles. In all, 821 consecutive ICSI cases were analysed retrospectively. While a significant linear decline in semen volume was detected, no significant differences in the concentration, motility or morphology of the spermatozoa were found with paternal ageing. A significant decline in the number of oocytes retrieved and the number of mature oocytes obtained was found with advancing maternal age. An increase in the occurrence of digyny was noted with parental ageing, while no difference in single or bipronuclear fertilization was found. Older women had a decreased incidence of single pronucleus formation and an increase in digyny, but no significant difference in the percentage of oocytes that underwent two-pronuclear fertilization was detected with regard to maternal ageing. Pregnancy outcomes were not influenced by the age of the male partner, while a strong negative correlation was found with maternal ageing. To better analyse male partner ageing as a factor affecting pregnancy outcome, we analysed a subgroup of patients with a female partner aged <35 years who underwent ICSI. No paternal influence on ICSI pregnancy outcome was found in this subgroup of patients. We conclude that the influence on pregnancy outcome after ICSI is related mostly to maternal and not paternal age.

Incisional hernias after laparoscopy.

Laparoscopy, using a two-puncture technique, has been used for a variety of gynecologic indications for more than two decades. The procedure is considered safe and effective, although rare complications, such as incisional hernias, have been reported. In this review, the issue of postlaparoscopic incisional hernias is discussed in terms of incidence, predisposing factors, time of appearance, and preventive measures. With the evolvement of operative laparoscopy, larger trocars and cannulas have been introduced, increasing the incidence of postlaparoscopic incisional hernias. Awareness of the possibility of this complication will lead to the use of proper surgical techniques, as suggested, while knowledge of the postoperative signs and symptoms will lead to early diagnosis and prevention of sequelae.

Treatment variables in relation to oocyte maturation: lessons from a clinical micromanipulation-assisted in vitro fertilization program.

OBJECTIVE: In an effort to understand the mechanism underlying the improved pregnancy rate observed in IVF cycles when gonadotropin-releasing hormone analogues (GnRH-a) are applied, we investigated a possible relationship between treatment variables and oocyte nuclear maturity. DESIGN: Nuclear maturity was retrospectively assessed in cumulus-free, denuded oocytes, obtained from women undergoing micromanipulation-assisted IVF treatment following controlled ovarian hyperstimulation with GnRH-a and menotropins. SETTING: The setting was the infertility and IVF unit of a tertiary academic medical center. PARTICIPANTS: Two hundred twenty-one patients underwent 435 treatment cycles. MAIN OUTCOME MEASURE: This was the proportion of germinal vesicle-intact immature (GVII) oocytes. RESULTS: One hundred fifty-four of the 3520 oocytes studied (4.4%) were in the GVII stage. These oocytes were found in 66 of the treatment cycles (15.2%) and in 54 of the patients (24.4%). Cycles in which GVII oocytes were detected did not differ from those in which all the aspirated oocytes were mature in the following respects: patient age, type and duration of infertility, controlled ovarian hyperstimulation protocol and time of ovum pickup. However, the GVII group was characterized by a significantly higher peak estradiol level, as well as a higher number of mature follicles visualized sonographically (diameter, > 14 mm) and oocytes retrieved. CONCLUSIONS: Comparing the present findings with previously published data, it appears that the inclusion of GnRH-a in the stimulation regimen is associated with a lower proportion of immature oocytes. A higher occurrence of oocyte-nuclear immaturity is apparently associated with a significantly better ovarian response to stimulation. The high incidence of immature oocytes observed in patients with normospermic partners and low fertilization rates in previous cycles may suggest that the fertilization failure in some of these cases is due to oocyte, rather than sperm, dysfunction.

Chorioamnionitis caused by gram-negative bacteria as an etiologic factor in preterm birth.

The role and microbiological causes of infection and inflammation of the chorioamnion were studied in 85 patients with spontaneous preterm deliveries (< 37 weeks) and in 85 control patients with full term deliveries. Microorganisms were isolated from the freshly separated chorioamnion in 55% of preterm and 26% of term deliveries (p < 0.001). Isolation rates of gram-negative enteric bacteria were significantly higher in preterm deliveries than in term deliveries (p < 0.001), whereas differences in the isolation of other bacterial species were not significant. Histological chorioamnionitis was noted in 49% of preterm and 14% of term deliveries (p < 0.001), and was strongly associated with a positive chorioamniotic culture in both groups (p < 0.001). Histological chorioamnionitis was noted in 94%, 54%, and 4% of membranes with gram-negative rods, other microbial species and negative cultures, respectively (p < 0.001). Preterm deliveries were also associated with significantly higher rates of bacterial vaginosis (38% vs. 14%) and isolation of vaginal pathogens (85% vs. 65%). In the case of the majority (88%) of chorioamniotic isolates the same species was isolated in the vagina. The findings suggest that gram-negative enteric rods are important placental pathogens responsible for sub-clinical chorioamnionitis and possibly preterm birth. The findings support the concept that microorganisms ascending from the lower genital tract produce local inflammation, which may result in preterm labour and delivery.

Human sperm cytosolic factor triggers Ca2+ oscillations and overcomes activation failure of mammalian oocytes.

Among the possible mechanisms of oocyte activation after sperm penetration, it appears most likely that a protein released by the spermatozoon elicits a calcium elevation in the ooplasm. To further test this idea, cytosolic factors obtained from human spermatozoa by two different methods, freezing-thawing and sonication, were injected into mouse oocytes following which intracellular calcium release was measured. Of a total of 42 mouse oocytes, a pattern of calcium oscillations was observed in nine out of 16 oocytes injected with sonicated fraction, in all of eight oocytes with the frozen-thawed fraction and in none of 18 control oocytes. Injection of the frozen-thawed fraction also produced regular calcium oscillations in all of five in-vitro matured human oocytes. To assess the putative factor's ability to support fertilization, human oocytes that were not activated by prior intracytoplasmic injection of spermatozoa (ICSI) and round spermatids were reinjected with the frozen-thawed sperm fraction. Of 23 human oocytes which remained unfertilized after ICSI, 19 became activated after injection with sperm cytosolic factor; eight showed two pronuclei, three one pronucleus and eight showed three or more pronuclei. Of 11 oocytes unfertilized after prior round spermatid injection, two developed two pronuclei, four developed one pronucleus and two had three or more pronuclei. Cytogenetic analysis by fluorescence in-situ hybridization confirmed the existence of a male pronucleus in eight out of nine such zygotes displaying two or more pronuclei. Thus, human sperm extracts activated mouse and human oocytes after injection, as judged by calcium flux patterns in conjunction with male pronucleus formation.

Acrosomal status of human spermatozoa after follicular fluid or calcium ionophore challenge in relation to semen parameters and fertilizing capacity in vitro.

The proportion of spermatozoa that undergo spontaneous acrosome reaction in vitro is relatively low. The proportion can be enhanced by incubation with either biological inducers such as follicular fluid or chemicals like calcium ionophore. It has been suggested that improper acrosomal reaction may be a cause of fertilization failure in vitro. The objectives of the present study were to assess the acrosomal status of human sperm following follicular fluid or calcium ionophore treatment and to analyse the relationship between spontaneous and induced acrosome reaction and fertilization rates in vitro by standard in vitro fertilization (IVF) technology. In all, 53 semen samples (22 normal and 31 subnormal) were studied. The effect of calcium ionophore A 23187 and follicular fluid was assessed using the fluorescence activated cell sorter. IVF results were evaluated in relation to the acrosome status of the sperm samples. Our results demonstrate that the effect of follicular fluid on the acrosomal status correlated positively with the effect obtained by the calcium ionophore (Pearson's correlation r = 0.45). A significantly higher percentage of maximal acrosome change (P < 0.02) was found in cases where fertilization occurred (19/27), than in sperm samples that did not achieve fertilization in vitro (8/27). The present finding that follicular fluid induced acrosome reaction can serve as a predictive tool which is as good as the ionophore treatment for assessing IVF outcome, supports the use of this method for clinical purposes.

The role of uterine straightening by passive bladder distension before embryo transfer in IVF cycles.

PURPOSE: The present study investigated the effect of bladder distension on in vitro fertilization and embryo transfer (IVF-ET) results. METHODS: The study comprised 796 patients after successful transvaginal oocyte pickup and IVF, who, on the basis of bladder filling for ET, were divided into two groups. In group E, 385 patients underwent ET with an empty bladder, and in group F, 411 patients underwent ET with a full bladder. RESULTS: Sixty-four pregnancies were achieved in group E (16.6%), compared to 110 pregnancies in group F (26.8%, P = 0.006). A similar pregnancy loss rate was observed in both groups, 13 in group E (20.3%) and 29 in group F (26.4%; P = NS). CONCLUSIONS: A significantly higher pregnancy rate was achieved with routine bladder distension before ET, probably attributable to the smooth and easy insertion of the ET catheter.

Augmentation of low ovarian response to superovulation before in vitro fertilization following priming with contraceptive pills.

Poor ovarian response to superovulation treatment is observed in a certain group of patients, the so-called 'low responders'. Despite the evolution of sophisticated controlled ovarian hyperstimulation (COH) regimens prior to the in vitro fertilization (IVF), the ideal stimulation protocol for the low responder has yet to be formulated. The objective of this study was to assess the effect of oral contraceptive pills (OCP), administered before the initiation of superovulation, on ovarian response and IVF treatment results in patients with previous 'low response' to exogenous gonadotropin stimulation. The study group comprised 42 patients who had exhibited poor ovarian response to standard superovulation protocols in at least two previous consecutive treatment attempts. Contraceptive pills were administered for 28-42 days and were immediately followed by menotropin treatment. The study group (n=50 cycles) was compared with the control group consisting of previous cycles (n=88) of the same women. Significant differences were noted in peak estradiol levels (983 +/- 739 vs. 517 +/- 249 pg/ml; P <0.01, paired Student's t test) and number of pre-ovulatory follicles between the study and the control groups. Thirty-three of the cycles (66%) reached the stage of ovum pick-up, compared with 22 (25%) of the previous IVF cycles in these women. The mean number of oocytes retrieved was 6.1 +/- 3.0 and 2.4 +/- 1.3 in the study and control groups, respectively (P <0.01; paired Student's t test). Embryo transfer (ET) was performed in 62% of the treatment cycles and resulted in five clinical pregnancies (16.1% per ET). No pregnancies were recorded in the control group. This study demonstrates the beneficial effect of OCP given prior to IVF treatment, and provides an efficient treatment modality for women who consistently respond poorly to standard COH protocols.

Intranasal nafarelin versus buserelin (short protocol) for controlled ovarian hyperstimulation before in vitro fertilization: a prospective clinical trial.

The aim of this study was to compare the effect of nafarelin acetate with that of buserelin acetate nasal spray, when administered in a 'short' protocol, as an adjunct to human menopausal gonadotropin (hMG) for controlled ovarian hyperstimulation before in vitro fertilization (IVF). Twenty-two IVF subjects were randomly recruited. Each underwent two consecutive treatment cycles; one with buserelin (900 micrograms/day) and another with nafarelin (400 micrograms/day). The treatment protocol included transnasal gonadotropin-releasing hormone (GnRH) analog from the second cycle day and hMG from the fourth day of the cycle. The buserelin and nafarelin cycles did not differ significantly in the following parameters: baseline hormone profile, duration of GnRH analog treatment, mean hMG dose required, peak estradiol levels, number of preovulatory follicles, number of aspirated oocytes, fertilization rate and number of transferred or frozen embryos. No side-effects or cancellations of treatment were recorded. The average dose required was lower for nafarelin and, because this analog was given only twice a day, it was more convenient to administer. These findings suggest that nafarelin is as effective as buserelin (when administered in a "short' protocol) in achieving controlled ovarian hyperstimulation. It even offers advantages over buserelin with respect to the total dose required (which probably reflects its relatively high potency) and the subjects' compliance.

The initial flare-up induced by gonadotropin releasing hormone agonist may serve as a predictor of ovarian response in the current IVF-ET treatment cycle in normogonadotropic women aged 40-48 years.

OBJECTIVE: Our purpose was to assess the potential role of the baseline hormone profile in combination with the initial pattern of response to gonadotropin releasing hormone (GnRH) analogue in predicting ovarian function and hence reproductive outcome in normogonadotropic patients aged 40 years or older undergoing IVF treatment. PATIENTS AND METHODS: A retrospective analysis of 394 controlled ovarian hyperstimulation (COH) cycles that reached the stage of oocyte retrieval was conducted. The study included 163 normogonadotropic (serum FSH < or = 15 IUIL) patients aged between 40 and 48 years who had regular menstrual cycles. Superovulation was achieved using menotropins in combination with GnRH analog (short protocol, beginning on menstrual day 2). The ovarian response was monitored on the third cycle day, the day following the first GnRH analogue administration. RESULTS: Cycle distribution by patient age was 175 (44.4%), 122 (30.9%), and 97 (24.7%), while the patient distribution was 85 (52.2%), 48 (29.5%), and 30 (18.3%) for age groups 40-41, 42-43, and 44-48 years, respectively. The mean total dose of menotropins needed for optimal COH was 1787 IU (range, 600-6000 IU). This dose increased with age, while the yield of oocytes and embryos declined (P < 0.05; ANOVA). A positive correlation was demonstrated between the E2 level on day 3 (GnRH analogue flare effect) and the outcome of the treatment cycle (number of oocytes and embryos). Using multiple stepwise regression analysis, it was demonstrated that the initial (day 3) serum E2 levels, combined with baseline FSH levels, patients's age and body mass index enabled early prediction of the ovarian response in the current IVF-ET treatment cycle (oocytes = 8.2 - 0.18 x Age + 0.17 x BMI - 0.12 x FSH + 0.0042 x E2). CONCLUSIONS: Multiple-parameter analysis demonstrated that the use of the initial E2 response to GnRH analogue stimulation combined with basic clinical data may assist in the prediction of ovarian function and hence the reproductive outcome in normogonadotropic IVF patients aged 40 years or older. This may serve as a clinical tool for improving patient selection and treatment outcome in IVF-ET.