Mustafa Bahceci

Conception rates following assisted reproduction in poor responder patients: a retrospective study in 300 consecutive cycles

Poor response to ovarian stimulation for assisted reproduction treatment is a therapeutic challenge. Oocyte donation may be unacceptable to some patients, and many couples opt to continue with treatment despite low follicle numbers. Minimal data are available regarding conception rates in poor responders who elect to undergo oocyte retrieval. This study summarizes the outcome of assisted reproduction treatment in poor responders who produced four or fewer oocytes during ovarian stimulation, in order to provide better counselling to such patients in the future. Embryo transfers were performed in 208 of 300 cycles demonstrating poor ovarian response. Pregnancy rate (PR) (15.9%) was significantly higher in patients in whom four oocytes were retrieved, compared with patients in whom one or two oocytes were retrieved (2.3 and 4.3% respectively). Younger patients (< or =34 years) had significantly higher PR (19.5%) compared with older patients (> or =35 and < or =39 years, PR 7.2% and > or =40 years, PR 1.5% respectively). One hundred and twenty-six age-matched normal responders in whom three embryos were transferred had higher implantation rates (15.3%) and PR (37.3%) compared with poor responders in whom three embryos were transferred (6.6 and 16.6% respectively; P < 0.05). In this regard, patient age, number of oocytes retrieved and number of embryos available for transfer determine prognosis for the success of IVF in patients who respond to ovarian stimulation with four or fewer follicles for assisted reproduction treatment.

Time-lapse evaluation of human embryo development in single versus sequential culture media—a sibling oocyte study

ObjectiveTo compare the dynamics of early development between embryos cultured in single and sequential media.DesignRandomized, comparative study.SettingPrivate IVF centre.PatientsA total of 446 metaphase II oocytes from 51 couples who underwent oocyte retrieval procedure for intracytoplasmic sperm injection. Forty-nine resulted in embryo transfer.InterventionOocytes were split between single and sequential media produced by the same manufacturer and cultured in a time-lapse incubator.Main outcome measuresMorphokinetic parameters until the embryos reached the 5-cell stage (t5), utilization, clinical pregnancy and implantation rates.ResultsEmbryos cultured in single media were advanced from the first mitosis cycle and reached 2- to 5-cell stages earlier. There was not any difference between the durations for cell cycle two (cc2 = t3-t2) and s2 (t4-t3). The utilization, clinical pregnancy and implantation rates did not differ between groups. The proportion of cryopreserved day6 embryos to two pronuclei oocytes was significantly higher in sequential than in single media.ConclusionsMorphokinetics of embryo development vary between single and sequential culture media at least until the 5-cell stage. The overall clinical and embryological parameters remain similar regardless of the culture system.

Does the estradiol level on the day of human chorionic gonadotrophin administration have an impact on pregnancy rates in patients treated with rec-FSH/GnRH antagonist?

BACKGROUND The purpose of this prospective observational study was to evaluate the association between estradiol (E(2)) levels on the day of human chorionic gonadotrophin (hCG) administration and pregnancy rates in a recombinant FSH (rec-FSH) antagonist fixed protocol. METHODS A group of 207 patients (<or=39 years of age), treated by IVF/ICSI, received 200 IU/day rec-FSH from Day 2 of the cycle and daily GnRH antagonist starting on Day 6 of stimulation. The criteria for hCG administration included only the presence of >or=3 follicles of >or=17 mm diameter. One to two embryos were transferred on Day 3 after oocyte retrieval. RESULTS The area under the curve (AUC) for E(2) on the day of hCG could not distinguish between pregnant and non-pregnant women (AUC:0.5; 95% confidence interval (CI): 0.42-0.59). No significant difference was observed between the three percentile groups of E(2) values on the day of hCG administration [group 1, lower 25th percentile (<1142 pg/ml); group 2, medium 50th percentile (1142-2446 pg/ml) and group 3, higher 75th percentile (>2446 pg/ml)] for the ongoing pregnancy rates (P = 0.52). On the contrary, the linear regression model showed that higher E(2) values on the day of hCG administration significantly improved the scores of transferred embryos (P = 0.01) as well as the total embryo score (P = 0.02). Yet subgroup analysis only in this high responders group revealed lower E(2) and progesterone levels on the day of hCG in pregnant women compared with the non-pregnant (P = 0.01). CONCLUSIONS E(2) concentrations on the day of hCG administration in GnRH antagonist cycles are not associated with pregnancy rates. A potential deleterious impact of estradiol on endometrial receptivity is shown for the high responders who have high E(2) levels and improved embryo quality without a concomitant rise in pregnancy rate.

In vitro culture under physiologic oxygen concentration improves blastocyst yield and quality: a prospective randomized survey on sibling oocytes

A prospective randomized study was carried on sibling oocytes in which human gametes and embryos were cultured at physiologic (6% CO(2) + 5% O(2) + 89% N(2)) condition from insemination to day 6 or at atmospheric (6% CO(2) in air) condition until day 3 and at physiologic environment afterward. The results showed that physiologic oxygen concentration throughout culture period improved total blastocyst yield and day 5 embryo quality.

Effect of Zinc Supplementation in a Turkish Woman with Two Previous Anencephalic Infants

The authors report a case of nutritional zinc deficiency in a young (18-year-old) Turkish woman, who previously delivered 2 anencephalic stillborn infants. The patient was supplemented with 22.5 mg oral zinc sulfate (100 mg ZnSO4.7H2O) for 5 months after her second delivery prior to her third pregnancy. Her blood (plasma and red blood cell) and hair zinc levels returned to normal following zinc supplementation. Good response to Zn supplementation was another criterion of Zn deficiency in this particular case. After an uneventful gestational period, she delivered an apparently normal full-term male child who has grown normally during the first 12 months.

Effect of oxygen concentration during the incubation of embryos of women undergoing ICSI and embryo transfer: a prospective randomized study

The hypothesis that ICSI outcome can be improved by culturing human embryos in an atmosphere of controlled O(2) concentration (5%) compared with 20% was tested in a prospective randomized study of 712 transfer cycles. The cycle characteristics and the embryology parameters were similar between groups. The embryo qualities were similar with day 2 transfers; however, they were better with day 3 transfers incubated in 5% O(2) than in 20% O(2). The clinical outcome parameters did not differ between groups according to the O(2) concentration. The results indicated that culture of embryos under atmospheric conditions of O(2) for the first 2 or 3 days did not alter the clinical outcome in ICSI cycles.

Klinefelter syndrome: does it confer a bad prognosis in treatment of nonobstructive azoospermia?

OBJECTIVE To determine the effectiveness of microsurgical testicular sperm extraction (micro-TESE) and intracytoplasmic sperm injection (ICSI) for men with Klinefelter syndrome (KS). DESIGN Retrospective clinical study. SETTING Private IVF center. PATIENT(S) Men with nonmosaic KS (n = 106), and men with nonobstructive azoospermia (NOA) and normal karyotypes (n = 379). INTERVENTION(S) Micro-TESE on the day of oocyte retrieval. MAIN OUTCOME MEASURE(S) Sperm recovery, fertilization, pregnancy, and spontaneous abortion rates. RESULT(S) Sperm was successfully recovered in 50 of 106 (47%) men in the KS group and 188 of 379 (50%) in the NOA group. The fertilization rate was higher in the NOA group than the KS group (65% vs. 57%, respectively); however, pregnancy (55% vs. 53%) and abortion rates (12% vs. 11.5%) did not differ statistically significantly between groups. In the KS group, 23 pregnancies resulted in 29 live births; the 21 children who underwent genetic evaluation had normal karyotypes. CONCLUSION(S) Sperm recovery rates in men with KS were similar to those of men with NOA and normal karyotypes. The fertilization rate was statistically significantly lower for men with KS than men with NOA, but pregnancy and abortion rates were similar. We observed good sperm recovery and ICSI outcomes for patients with KS.

Exome sequencing reveals a nonsense mutation in TEX15 causing spermatogenic failure in a Turkish family

Infertility is a global healthcare problem, and despite long years of assisted reproductive activities, a significant number of cases remain idiopathic. Our currently restricted understanding of basic mechanisms driving human gametogenesis severely limits the improvement of clinical care for infertile patients. Using exome sequencing, we identified a nonsense mutation leading to a premature stop in the TEX15 locus (c.2130T>G, p.Y710*) in a consanguineous Turkish family comprising eight siblings in which three brothers were identified as infertile. TEX15 displays testis-specific expression, maps to chromosome 8, contains four exons and encodes a 2789-amino acid protein with uncertain function. The mutation, which should lead to early translational termination at the first exon of TEX15, co-segregated with the infertility phenotype, and our data strongly suggest that it is the cause of spermatogenic defects in the family. All three affected brothers presented a phenotype reminiscent of the one observed in KO mice. Indeed, previously reported results demonstrated that disruption of the orthologous gene in mice caused a drastic reduction in testis size and meiotic arrest in the first wave of spermatogenesis in males while female KO mice were fertile. The data from our study of one Turkish family suggested that the identified mutation correlates with a decrease in sperm count over time. A diagnostic test identifying the mutation in man could provide an indication of spermatogenic failure and prompt patients to undertake sperm cryopreservation at an early age.

Gonadotrophin therapy in combination with ICSI in men with hypogonadotrophic hypogonadism

The aim of this study was to evaluate the impact of gonadotrophin therapy in combination with intracytoplasmic sperm injection (ICSI) in men with hypogonadotrophic hypogonadism (HH). Twenty-five azoospermic men were diagnosed with HH due to low FSH, LH and total testosterone concentrations. These patients were treated with human chorionic gonadotrophin for 1 month plus recombinant FSH the following month. Total testosterone concentrations were measured in the first and third months. Semen analyses were performed monthly after the third month of treatment. ICSI was performed when sperm production commenced. Total testosterone concentration and testicular volume were significantly increased after gonadotrophin therapy (P < 0.001). On average, spermatozoa were detected in the ejaculate after 10 months. Spontaneous pregnancies were achieved in four couples. Twenty-two ICSI cycles were performed in 18 couples using ejaculated or testicular spermatozoa, and 12 pregnancies (54.5% per cycle) were achieved. These results showed that HH could be treated successfully with hormonal therapy combined with ICSI using ejaculated spermatozoa. The use of ICSI made it possible to achieve pregnancy when spermatozoa appeared in the ejaculate, and shortened the duration of gonadotrophin therapy.

Bilateral internal jugular venous thrombosis following successful assisted conception in the absence of ovarian hyperstimulation syndrome

The majority of the venous thromboembolic events seen in patient following gonadotropin administration were associated with the development of ovarian hyperstimulation syndrome (OHSS). However, in this case report, a 29-year-old woman that conceived by controlled ovarian hyperstimulation, intracytoplasmic sperm injection and subsequent embryo transfer without conjunction of OHSS was described. Bilateral jugular venous thrombi were detected by duplex Doppler in the 8th week of pregnancy when she was admitted to the emergency room for difficulty in swallowing and bilateral neck pain. She had unremarkable history and negative results for thrombophilia screening. Full anticoagulation with intravenous heparin was initiated and continued subcutaneously throughout pregnancy. She delivered two healthy babies at 36 weeks of pregnancy. Venous thromboembolism should be taken in account in patients undergoing gonadotropin administration for assisted conception with the complaint of extremity pain regardless of having risk factors for thromboembolism.