Sezcan Mumusoglu

Preparation of endometrium for frozen embryo replacement cycles: a systematic review and meta-analysis.

PurposeThe purpose of this study was to evaluate the best protocol to prepare endometrium for frozen embryo replacement (FER) cycles.MethodsThis study is a systematic review and meta-analysis. Following PubMed and OvidSP search, a total of 1166 studies published after 1990 were identified following removal of duplicates. Following exclusion of studies not matching our inclusion criteria, a total of 33 studies were analyzed. Primary outcome measure was live birth. The following protocols, including true natural cycle (tNC), modified natural cycle (mNC), artificial cycle (AC) with or without suppression, and mild ovarian stimulation (OS) with gonadotropin (Gn) or aromatase inhibitor (AI), were compared.ResultsNo statistically significant difference for both clinical pregnancy and live birth was noted between tNC and mNC groups. When tNC and AC without suppression groups are compared, there was a statistically significant difference in clinical pregnancy rate in favor of tNC, whereas it failed to reach statistical significance for live birth. When tNC and AC with suppression groups are compared, there was a statistically significant difference in live birth rate favoring the latter. Similar pregnancy outcome was noted among mNC versus AC with or without suppression groups. Similarly, no difference in clinical pregnancy and live birth was noted when ACs with or without suppression groups are compared.ConclusionsThere is no consistent superiority of any endometrial preparation for FER. However, mNC has several advantages (being patient-friendly; yielding at least equivalent or better pregnancy rates when compared with tNC and AC with or without suppression; may not require LPS). Mild OS with Gn or AI may be promising.

The impact of unilateral salpingectomy on antral follicle count and ovarian response in ICSI cycles: comparison of contralateral side

Abstract Objective: To determine the impact of salpingectomy on the ovarian reserve. Comparisons are made with the contralateral side in patients with unilateral salpingectomy undergoing intracytoplasmic sperm injection (ICSI) cycles. Study design: Patients under 40 with unilateral salpingectomy and without history of ovarian surgery were selected for the multicentre retrospective study. Women with bilateral salpingectomy and history of endometriosis were excluded from the study. Antral follicle count, controlled ovarian hyperstimulation (COH) parameters and number of collected oocytes were the main outcome measures of the study. Results: A total of 56 patients were eligible for this study. The mean age of the patients was 31.6 ± 4.7 years. The reasons for the salpingectomy were hydrosalpinx (39.3%, n = 22) and ruptured ectopic pregnancy (60.7%, n = 34). The ongoing pregnancy rate per embryo transfer was 30.6%. There was no statistically significant difference between the operated and non-operated sides in antral follicle count (AFC), follicles  ≥ 17 mm and 10–17 mm on day of human chorionic gonadotrophin (hCG), or number of aspirated oocytes. In the subgroup analysis, AFC, number of growing follicles on day of hCG and number of collected oocytes were comparable between the ectopic pregnancy group and hydrosalpinx group. Conclusion: The study suggests that salpingectomy is not associated with detrimental effects on AFC and ovarian response.

Prenatal Diagnosis of Hemoglobinopathies in Hacettepe University, Turkey

Between 1983 and 2008, prenatal diagnostic procedures for identifying hemoglobinopathies were performed in 947 at-risk fetuses. Seventy-six percent of the fetuses were at risk for β-thalassemia major and 16% for sickle cell anemia; only a small percentage (7%) were at risk for compound heterozygosity of β-thalassemia and an abnormal hemoglobin of the β chain. The results of the study showed that β gene mutations in hemoglobinopathies have a very broad spectrum. Seven hundred and thirty of the 947 fetuses examined using the DNA technique showed 88 different combinations of 27 different mutations. Although the number of fetuses evaluated was far below the desired target, the termination of 261 affected fetuses provided both psychological and economic relief for the parents and was economically beneficial for the country in the long term.

Does the presence of autoantibodies without autoimmune diseases and hereditary thrombophilia have an effect on recurrent pregnancy loss

Abstract Objective: To assess whether the presence of autoantibodies has any effect on recurrent pregnancy loss (RPL) and obstetric complications in women who do not have autoimmune diseases and hereditary thrombophilia. Methods: Retrospectively, 515 patients who underwent antibody investigation with anti-nuclear antibody, extractable nuclear antigen, anti-double stranded DNA, anti-parietal cell, anti-smooth muscle, anti-mitochondrial (AMA), anti-thyroid peroxidase, anti-thyroglobulin (anti-TG) and anti-phospholipid (aPL) at Hacettepe University were included. Of those patients, 212 had one or more autoantibodies whereas the remaining 303 were negative for all autoantibodies. RPL was the primary outcome and was defined as ≥2 pregnancy losses (n = 119). Results: The frequency of RPL was significantly higher in the autoantibody positive group than controls (28.3% versus 14.5%, p<0.001). Anti-TG (21.2% versus 7.8%, p < 0.001), aPL (18.3% versus 5.6%, p < 0.001) and AMA (4.8% versus 0.5%, p = 0.001) antibodies were more common in patients with RPL. For the view of obstetric complications, oligohydramniosis (3.8% versus 0.7%, p = 0.03) and stillbirth (17.0% versus 10.6%, p = 0.002) were significantly higher in the autoantibody-positive group. Conclusions: Even in women without autoimmune disease or hereditary thrombophilia, autoantibodies per se might directly increase the risk of RPL and obstetric complications. The screening anti-TG and aPL autoantibodies in the first step might be considered in patients with RPL.

Duration of blastulation may be associated with ongoing pregnancy rate in single euploid blastocyst transfer cycles

Not all euploid embryos implant, necessitating additional tools to select viable blastocysts in preimplantation genetic screening cycles. In this retrospective cohort study, 129 consecutive patients who underwent 129 single euploid blastocyst transfers in cryopreserved embryo transfer cycles were included. All embryos were individually cultured in a time-lapse incubator from intracytoplasmic sperm injection up to trophoectoderm biopsy. Twenty-three time-lapse morphokinetic variables were tested among patients with (n = 68) or without (n = 61) ongoing pregnancy. All 23 time-lapse morphokinetic variables, apart from duration of blastulation (tB-tSB), were comparable between patients with or without ongoing pregnancy. Duration of blastulation was significantly shorter in patients with ongoing pregnancy (8.1 ± 3.2 versus 9.5 ± 3.4 h; P = 0.014); shorter duration of blastulation remained an independent predictor for ongoing pregnancy, when tested by logistic regression analysis (OR 0.81; 95% CI 0.70 to 0.93). One important limitation of this study, and a reason for caution, is the use of multiple comparisons, which can lead to differences at the 0.05 level simply by chance or random variation. Nonetheless, the study suggests that when more than one euploid blastocyst is available, priority might be given to those with a shorter duration of blastulation.

Which is worse? Comparison of ART outcome between women with primary or recurrent endometriomas

STUDY QUESTİON Are live birth rates (LBR) different after ART cycles between women with primary or recurrent endometrioma? SUMMARY ANSWER Women with recurrent endometrioma have similar LBR as compared to patients with primary endometrioma. WHAT IS ALREADY KNOWN Recurrence rate can be as high as 29% after endometrioma excision. Prior studies on management of endometrioma before ART involve primary endometriomas. There is limited information regarding the prognosis of women with recurrent endometriomas. STUDY DESIGN, SIZE, DURATION A multicenter retrospective cohort study, including 76 women with primary and 82 women with recurrent endometriomas treated at the participating centers over a 6-year period. PARTICIPANTS/MATERIALS, SETTING, METHODS Women with endometrioma who underwent ART at three academic ART centers. Couples with another indication for ART were excluded. MAIN RESULTS AND THE ROLE OF CHANCE Female age, median number of prior failed ART cycles, proportion of patients with bilateral endometrioma (28 versus 28.9%), ovarian stimulation protocols, and total gonadotropin consumption were similar between the study groups. Numbers of metaphase two oocytes (5 versus 6), number of embryos transferred, and the proportion of patients undergoing blastocyst transfer were similar across the study groups. Clinical pregnancy rates (36.6 versus 34.2%, absolute difference 2.4%, 95% CI: -12.5 to 17.3%, P = 0.83) and LBR (35.4 versus 30.3%, absolute difference 5.1%, 95% CI: -9.5 to 19.7%, P = 0.51) per started cycle in recurrent and primary endometrioma were similar. Comparable success rates were also confirmed with logistic regression analysis (OR: 1.14, 95% CI: 0.78-0.57, P = 2.3). LIMITATIONS, REASONS FOR CAUTION The retrospective design has inherent limitations. Some women with severely decreased ovarian reserve after primary endometrioma excision may not have pursued further treatment. WIDER IMPLICATIONS OF THE FINDINGS The management of endometrioma prior to ART is controversial but a different management strategy is not required for recurrent endometriomas. Since recurrent endometriomas do not have a worse impact on ART outcome than primary endometriomas, and repeat surgery has a higher risk for complications, conservative management without surgery can be justified. STUDY FUNDING/COMPETING INTEREST(S) No funding or competing interests to declare. TRIAL REGISTRATION NUMBER None.

A Case of Placenta Increta Mimicking Submucous Leiomyoma

In recent years with the increase in cesarean section rates, the frequency of placenta accreta cases rises. It causes 33–50% of all emergency peripartum hysterectomies. We present a 42-year-old case who was caught with early postpartum hemorrhage due to retained placental products. The ultrasonography showed a 65 × 84 mm mass in the uterine cavity after the delivery. Due to presence of early postpartum hemorrhage which needs transfusion, an intervention decision was made. The patient underwent curettage but the mass could not be removed so that placental retention was ruled out. Submucous leiomyoma was made as first-prediagnosis. Hysterectomy operation was performed as a curative treatment. Placenta increta diagnosis was made as a final diagnosis with pathological examination. As a result, placental attachment disorders may be overlooked if it is not a placenta previa case.

The Impact of a Long-Acting Oral Sphingosine-1-Phosphate Analogue on Ovarian Aging in a Rat Model

In animal studies, intravenous continuous infusion or peritoneal injection of sphingosine-1-phosphate (S1P) has been shown to decrease chemotherapy- and radiotherapy-induced apoptosis on primordial follicles. Although a long-acting oral form of an S1P analogue (FTY720, fingolimod) has been recently developed and utilized in women with multiple sclerosis, there are no data exploring its ability to avoid spontaneous follicle apoptosis. Thirty 10-month-old female rats were randomly assigned to 3 groups to investigate whether fingolimod would be able to decrease the spontaneous ovarian follicle apoptosis ratio. An oral analogue form of S1P was administered for 60 days at a dose of 0.1 mg/kg (n = 10) or dose of 1 mg/kg (n = 10) per day. The control group (n = 10) received physiological serum via an orogastric feeding tube. The main outcome measures were anti-Müllerian hormone (AMH) level and nonapoptotic follicle ratio. While low-dose S1P group had comparable AMH levels to high-dose S1P group and controls, high-dose S1P group had higher mean levels of AMH, reaching marginal significance with controls (5.72 ± 0.61 vs 4.81 ± 0.85 ng/mL, P = .050). For the nonapoptotic primordial follicle ratio, both low-dose S1P group (67.0% ± 16.4% vs 29.9% ± 19.5%, P < .001) and high-dose S1P group (51.1% ± 11.5% vs 29.9% ± 19.5%, P = .023) had superior rates when compared with controls. Interestingly, low-dose S1P groups also had a statistically higher nonapoptotic primordial follicle ratio than high-dose S1P group (P = .047). Our findings suggest that a long-acting oral analogue of S1P might decrease spontaneous follicular apoptosis based on the nonapoptotic primordial follicle ratio and AMH levels when compared with placebo.

The comparison of the degree of apoptosis in ovaries and fallopian tubes between two different surgical interventions for tubal ligation: a rat-model

OBJECTIVE To compare the degree of apoptosis in ovaries and tubal epithelium observed secondary to tubal ligation either by Pomeroys method or bipolar electrocauterization in a rat model. MATERIAL AND METHODS A total of 24 female Sprague-Dawley rats were randomly assigned into 3 study groups: control (n=8), Pomeroy (n=8), and the electrocauterization group (n=8). Apoptotic cells were detected on the primary, secondary, tertiary follicles of the ovaries, and on the tubal epithelium using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling. The apoptotic index was calculated for each group by the percentage of the stained cells. RESULTS The apoptotic index of tubal epithelium was significantly higher in the bipolar electrocauterization group compared with the control and Pomeroy groups (3.1±0.8 vs. 1.4±1.0, p=0.018 and 2.0±1.2, p=0.03, respectively) whereas there was no significant difference between Pomeroys method and the control group. The apoptotic index of primary follicles was higher in the bipolar electrocauterization group compared with the control and Pomeroys method groups (3.4±0.5 vs. 1.2±0.4, p<0.001 and 1.8±0.8, p=0.005, respectively), but there was no significant difference between Pomeroys method and the control group. The apoptotic index of secondary and tertiary follicles was similar for each group. CONCLUSION Pomeroys technique, as a permanent contraception method, is associated with lower apoptotic index on ovary and fallopian tube when compared with bipolar electrocauterization.Objective: To compare the degree of apoptosis in ovaries and tubal epithelium observed secondary to tubal ligation either by Pomeroy’s method or bipolar electrocauterization in a rat model. Material and Methods: A total of 24 female Sprague-Dawley rats were randomly assigned into 3 study groups: control (n=8), Pomeroy (n=8), and the electrocauterization group (n=8). Apoptotic cells were detected on the primary, secondary, tertiary follicles of the ovaries, and on the tubal epithelium using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling. The apoptotic index was calculated for each group by the percentage of the stained cells. Results: The apoptotic index of tubal epithelium was significantly higher in the bipolar electrocauterization group compared with the control and Pomeroy groups (3.1±0.8 vs. 1.4±1.0, p=0.018 and 2.0±1.2, p=0.03, respectively) whereas there was no significant difference between Pomeroy’s method and the control group. The apoptotic index of primary follicles was higher in the bipolar electrocauterization group compared with the control and Pomeroy’s method groups (3.4±0.5 vs. 1.2±0.4, p<0.001 and 1.8±0.8, p=0.005, respectively), but there was no significant difference between Pomeroy’s method and the control group. The apoptotic index of secondary and tertiary follicles was similar for each group. Conclusion: Pomeroy’s technique, as a permanent contraception method, is associated with lower apoptotic index on ovary and fallopian tube when compared with bipolar electrocauterization.

Does pituitary suppression affect live birth rate in women with congenital hypogonadotrophic hypogonadism undergoing intra-cytoplasmic sperm injection? A multicenter cohort study

Abstract In this retrospective multicenter cohort study, women with congenital hypogonadotrophic hypogonadism (CHH) (n = 57) who underwent intra-cytoplasmic sperm injection in-between 2010–2014 were compared to age-matched controls with tubal factor infertility (n = 114) to assess ovarian stimulation cycle and pregnancy outcomes. Live birth rates (LBRs) per started cycle were 31.6 and 24.6% in CHH and controls groups, respectively (p = 0.36). Comparable success rates were also confirmed with the logistic regression analysis (OR: 1.44, 95% CI: 0.78–2.67, p = 0.24). Of the 57 women with CHH, 19 were stimulated with the gonadotropin-releasing hormone (GnRH) antagonist protocol, 13 with the long-GnRH-agonist protocol. Pituitary suppression (PS) was not employed in the remaining 25 cases. Compared to women with PS, women without PS had significantly higher embryo implantation rates (21.6 versus 52.6%, p = 0.03). Although there was a trend favoring no PS, LBRs (25.0 versus 40.0%, p = 0.26) per cycle were short of statistical significance. LBRs per cycle (57.1 versus 31.2%, p = 0.11) and miscarriage rates (11.1 versus 16.7%, p = 0.75) were similar between CHH women who were given estrogen + progesterone and progesterone alone to support the luteal phase. In conclusion, the optimal stimulation protocol appears to be exogenous gonadotropin stimulation alone, without PS, and progesterone-only luteal phase support in CHH patients.