Live birth in a 50-year-old woman following in vitro fertilization-embryo transfer with autologous oocytes: a rare case report.

OBJECTIVE: To report a live birth with in vitro fertilization (IVF) from a 50-year-old woman with homologous oocytes. DESIGN: Case report. SETTING: Referral center. PATIENT(S): A 50-year-old woman. INTERVENTION(S): IVF with fresh embryo transfer (ET). MAIN OUTCOME MEASURE(S): Live birth after IVF. RESULT(S): A 50-year-old woman conceived with her own oocytes by means of IVF. Three fresh embryos were transferred, resulting in a pregnancy and delivery by cesarean section at 35 weeks of a healthy male baby weighing 2,300 g. CONCLUSION(S): Extensive literature search suggests that this is the first case report of live birth in a 50-year-old woman after IVF-ET with her own oocytes. This is a very rare and unusual case that deviates from the norm and therefore warrants attention. In selected cases, assisted reproductive technology might be reasonable to try for a limited number of times with a woman's own oocytes.

Congenital malformations among babies born following letrozole or clomiphene for infertility treatment.

CONTEXT: Clomiphene citrate (CC) is the first line drug for ovulation induction but because of its peripheral antiestrogenic effect, letrozole was introduced as the 2nd line drug. It lacks the peripheral antiestrogenic effect and is associated with similar or even higher pregnancy rates. Since letrozole is a drug for breast cancer, its use for the purpose of ovulation induction became controversial in the light of studies indicating an increased incidence of congenital malformations. AIMS: To evaluate and compare the incidence of congenital malformations among offsprings of infertile couples who conceived naturally or with clomiphene citrate or letrozole treatment. SETTINGS AND DESIGN: A retrospective cohort study done at a tertiary infertility centre. METHODS AND MATERIAL: A total of 623 children born to infertile women who conceived naturally or following clomiphene citrate or letrozole treatment were included in this study. Subjects were sorted out from medical files of both mother and newborn and follow up study was done based on the information provided by parents through telephonic conversations. Babies with suspected anomaly were called and examined by specialists for the presence of major and minor congenital malformations. Other outcomes like multiple pregnancy rate and birth weight were also studied. RESULTS: Overall, congenital malformations, chromosomal abnormalities were found in 5 out of 171 (2.9%) babies in natural conception group and 5 out of 201 babies in the letrozole group (2.5%) and in 10 of 251 babies in the CC group (3.9%). CONCLUSIONS: There was no significant difference in the overall rate of congenital malformations among children born to mothers who conceived naturally or after letrozole or CC treatment. KEY MESSAGES: Congenital malformations have been found to be comparable following natural conception, letrozole and clomiphene citrate. Thus, the undue fear against letrozole may be uncalled for.

Assessment of sub-endometrial blood flow parameters following dydrogesterone and micronized vaginal progesterone administration in women with idiopathic recurrent miscarriage: a pilot study.

AIM: To evaluate differences in uteroplacental blood flow and pregnancy outcome in women with idiopathic recurrent spontaneous miscarriage (IRSM) following administration of micronized vaginal progesterone and oral dydrogesterone. METHODS: One hundred and thirty-three women (aged 23-40 years) who had had early miscarriages and spontaneous conception participated. Oral dydrogesterone (group A, n = 51) and micronized vaginal progesterone (group B, n = 50) were administrated for luteal support and compared. Pregnant women without history of recurrent miscarriage served as controls (group C, n = 32). The outcome measures consisted of endometrial blood flow parameters by Doppler indices and ongoing pregnancy rate. RESULTS: Before progesterone supplementation, resistivity index (RI) and pulsatility index (PI) were found to be significantly higher in groups A and B as compared to controls. Although statistically not significant, end diastolic velocity (EDV) and systolic/diastolic (S/D) ratio was found to be superior in controls than IRSM women. Peak systolic velocity (PSV) was comparable between IRSM and non-IRSM groups. Following progesterone supplementation, groups A and B showed a highly significant reduction in RI, PI and an increase in EDV. A relative increase in the value of PSV was observed in group A as compared to group B. There was remarkable difference in S/D in both groups. Although not statistically significant, group C showed reduction in RI, PI, PSV, EDV and S/D ratio. Pregnancy salvage rates were higher in group A (92.0%) as compared to group B (82.3%). CONCLUSION: Progesterone supplementation appears to lower vascular resistance in women with IRSM. Oral dydrogesterone appears to be equally effective in improving endometrial blood flow as compared with micronized progesterone.

Endometrial receptivity markers in infertile women stimulated with letrozole compared with clomiphene citrate and natural cycles.

Though various advantages associated with the use of letrozole as an ovulation inducing drug are documented, there is inadequate information regarding its effect on endometrial receptivity. Expression of endometrial receptivity markers including αvß3 integrin, L-selectin, LIF, and pinopods during the implantation window in infertile women stimulated with letrozole or clomiphene citrate (CC), and spontaneous cycles is investigated. A total of 36 women were included in the study out of which 16 women were diagnosed with primary unexplained infertility and the other 20 women with severe oligoasthenozoospermic/azoospermic male partners. Both groups were sub-divided into three groups; women stimulated with letrozole, or with CC, and the third group was allowed to ovulate spontaneously (natural cycles). Women having natural cycles and not given any drug were considered as controls. Once ovulation was confirmed by ultrasonography, endometrial samples were collected on the seventh day post-ovulation and analyzed. In women with unexplained infertility treated with letrozole and CC, epithelial and stromal expression of αvß3 integrin, L-selectin, leukemia inhibitory factor (LIF), and pinopod formation was found to be significantly higher as compared to controls. Expression of these receptivity markers was found to be comparable amongst the letrozole, CC, and control groups in women with severe oligoasthenozoospermic/azoospermic male partners. Cell cycle analysis showed similar cell cycle phase fractions on comparing the CC and the letrozole groups. Stimulation with letrozole and CC appears to enhance endometrial receptivity in women with unexplained infertility. However, letrozole and CC did not have any significant effect on the endometrial receptivity markers of women with severe oligoasthenozoospermic/azoospermic male partners.

Recurrent implantation success in consecutive embryo transfer cycles: a unique case report.

We describe here a unique case of a woman with an azoospermic male partner conceiving each time during ten consecutive in-vitro fertilization embryo transfer (IVF-ET) cycles. A 27 year old woman reported with primary infertility to our out-patient department at the Institute of Reproductive Medicine, Salt Lake, India in November 2001. Ten consecutive IVF-ET cycles including both, fresh and frozen embryos were performed over a span of ten years. Following each ET, the woman became pregnant; however, viable babies were not achieved. Finally, after the tenth consecutive IVF-ET cycle, a caesarean section (CS) was performed at 30 weeks and twin babies weighing 1.3 kg and 1.25 kg, respectively, were delivered and both the babies survived. It seems unlikely that the woman's conception with each embryo transfer was merely coincidental; a persistently receptive window of implantation with a high embryo implantation rate is evident. This case motivated us to introduce the term, repeated implantation success (RIS). We hypothesize that for successful implantation, expression of various factors during each cycle may be possible only in genetically pre-determined women. Identification of these genetically pre-determined set of marker(s) could help in predicting the chances of a successful pregnancy in women undergoing IVF.

Comparison of oral dydrogestrone with progesterone gel and micronized progesterone for luteal support in 1,373 women undergoing in vitro fertilization: a randomized clinical study.

OBJECTIVE: To compare the efficacy of oral dydrogesterone with that of micronized vaginal P gel and micronized P capsule for luteal supplementation. DESIGN: Prospective, randomized clinical study. SETTING: Institute of Reproductive Medicine, Kolkata, India. PATIENT(S): A total of 1,373 infertile women undergoing IVF participated. INTERVENTION(S): Micronized P gel, P capsule, and oral dydrogesterone were administered for luteal support and compared. MAIN OUTCOME MEASURE(S): Demographic profile and pregnancy and miscarriage rates. RESULT(S): The overall pregnancy rate and miscarriage rate were comparable among the three groups. CONCLUSION(S): Oral dydrogesterone seems to be a promising drug for luteal support in woman undergoing IVF.

Analysis of spindle characteristics and embryo quality in mice stimulated with letrozole using Polscope imaging.

OBJECTIVE: To explore the effect of letrozole as an ovulation inducing agent on oocyte and embryo quality in mice model. DESIGN: Prospective study. SETTING: Institute of Reproductive Medicine, Kolkata, India. ANIMAL(S): Sixty-nine sexually mature female Swiss Albino mice 6-7 weeks old. INTERVENTION(S): Metaphase II (MII) oocytes from two groups of mice, one group injected with letrozole and the other with rFSH. MAIN OUTCOME MEASURE(S): Number of MII oocytes, number of oocytes with meiotic spindle (MS), different angles of MS relative to the polar body (PB), spindle characteristics, and fertilization outcome. RESULT(S): The MS was present in 84% and 71.2% of the oocytes in the letrozole and rFSH group, respectively. In the letrozole group, 73% of the oocytes had a 0 degrees spindle position compared with 35.7% in the rFSH group. With letrozole, 19% of the oocytes had 0 degrees > MS < 90 degrees and 8% had MS >90 degrees , compared with 46.1% oocytes with 0 degrees > MS < 90 degrees and 18.2% with MS >90 degrees with rFSH. Mean spindle area retardance, spindle dimensions, and 4-8-cell embryo formation rate were significantly higher with letrozole compared with rFSH. Two-cell and blastocyst formation rates were similar in both groups. CONCLUSION(S): Robust birefringent spindles were obtained in mice on superovulation with letrozole. Letrozole does not appear to increase the risk of spindle assembly and preimplantation developmental arrest in mouse oocytes.

Comparison of letrozole with continuous gonadotropins and clomiphene-gonadotropin combination for ovulation induction in 1387 PCOS women after clomiphene citrate failure: a randomized prospective clinical trial.

PURPOSE: Letrozole, though reported to be an effective ovulation inducing agent, warrants larger randomized trials. The purpose of this study is to compare the efficacy of letrozole with that of rFSH and clomiphene citrate(CC)/rFSH for ovarian stimulation in IUI cycles. METHODS: Randomized, prospective, single-blinded clinical trial. 1387 PCOS women after CC failure were randomized into three groups: Group A received letrozole, Group B received CC with two doses rFSH and Group C received continuous rFSH day 2 onwards until hCG injection. RESULTS: Group A, B and C had an ovulation rate of 79.30%, 56.95% and 89.89% and cycle cancellation rate of 20.70%, 43.05% and 10.11%, respectively. Pregnancy rates in Group A, B and C were 23.39%, 14.35% and 17.92%, while the miscarriage rates were 13.80%, 16.67% and 14.52%, respectively. CONCLUSION: Letrozole appears to be a suitable ovulation inducing agent in PCOS women with CC failure and is found to be most effective when baseline estradiol level >60 pg/ml.

Luteal phase estradiol level: a potential predictive marker for successful pregnancy in in vitro fertilization/intracytoplasmic sperm injection.

OBJECTIVE: To analyze the role of luteal E(2), P, and FSH levels in the prediction of clinical pregnancy in stimulated cycles. DESIGN: Prospective study. SETTING: Institute of Reproductive Medicine, Salt Lake, Kolkata, India. PATIENT(S): A total of 268 women aged <40 years undergoing their first IVF-ET/intracytoplasmic sperm injection cycles. INTERVENTION(S): Estimation of luteal phase serum E(2), P, and FSH levels on days 0, 7, and 14 of ET. MAIN OUTCOME MEASURE(S): Comparison of luteal phase hormonal profile in pregnant and nonpregnant women and interpretation by discriminant analysis. RESULT(S): A total of 113 pregnancies were achieved (42.16%). Age, basal FSH level, peak E(2) level, number of oocytes retrieved, and number of embryos transferred were comparable between pregnant and nonpregnant women. Day-7 and day-14 luteal E(2) levels were significantly different between the two groups. Progesterone levels were comparable in both groups on days 0 and 14. Levels of FSH showed statistically significant differences between the two groups on days 0, 7, and 14. Classification accuracy for E(2), P, and FSH was 82.1%, 60.8%, and 67.51%, respectively. CONCLUSION(S): Luteal E(2) concentration seems to be a promising marker of successful clinical pregnancy.

Surgical correction of rare Müllerian anomalies and spontaneous pregnancies: a case report.

OBJECTIVE: To surgically reconstruct rare Müllerian duct anomalies with varying degrees of bladder exstrophy and congenital absence of ampullary portion of fallopian tube. DESIGN: Case report. SETTING: Institute of Reproductive Medicine, Salt Lake, Kolkata, India. PATIENT(S): Two cases of anteriorly displaced vagina with stenotic introitus, divergent pubic rami, and varying degrees of bladder exstrophy (group A) and three cases of congenital absence of ampullary portion of the fallopian tube with intact but blind fimbria attached to mesoovarium (group B). INTERVENTION(S): Introitoplasty and tubal anastomosis were performed for groups A and B, respectively. MAIN OUTCOME MEASURE(S): Description and treatment of two types of patients with rare Müllerian anomalies. RESULT(S): Three spontaneous pregnancies and viable deliveries, two in group A and one in group B, were achieved after surgical reconstruction. CONCLUSION(S): Assisted reproductive technologies usually provide a solution to infertility in rare Müllerian anomalies; reconstructive surgical procedures specific to the type of anatomical defect may also be considered for spontaneous pregnancy with viable deliveries.

Role of latent genital tuberculosis in repeated IVF failure in the Indian clinical setting.

Genital tuberculosis is reported to be a major pelvic factor causing infertility in Indian women and often exists without any apparent signs and symptoms. The role of latent tuberculosis in repeated IVF failure in unexplained infertility is examined. 81 women with unexplained infertility having repeated IVF failure tested for Mycobacterium tuberculosis using PCR, ZN staining and BACTEC-460 culture were selected. Fresh IVF-ET or frozen embryo transfer (FET) was attempted on patients successfully treated with anti-tubercular drugs (ATD). ATD-treated fresh cycles (group A1) and frozen cycles (group B1) were compared to previously failed fresh cycles (group A2) and FET attempts (group B2), respectively. Main outcome measures were gonadotropin required, terminal E2, number of oocytes retrieved, fertilization rate, embryo quality, endometrial thickness and sub-endometrial blood flow (V(max)). Gonadotropin required in group A1 was significantly less as compared to group A2. Number of oocytes retrieved and grade I embryos, endometrial thickness and V(max) were significantly higher in group A1. Endometrial thickness and V(max) were significantly increased in group B1 as compared to B2. The study indicates that latent tuberculosis should be considered in young Indian patients presenting with unexplained infertility with apparently normal pelvic and non-endometrial tubal factors and repeated IVF failure.