Onur Karabacak

The incidence of congenital malformations in a Turkish population

Objective: To determine the incidence and types of congenital anomalies in a Turkish population. Method: The total number of neonates (9160) born in the Department of Obstetrics and Gynecology, Gazi University Faculty of Medicine during 1988–1995 were studied retrospectively. Newborns with congenital anomaly were identified from their birth registries. The total incidence, types and combined anomalies were determined. Also, the relationship between congenital anomalies and maternal age and/or gender were investigated. For statistical evaluation, Chi‐square test, Yates correction and Fishers exact tests were used where appropriate. Results: The overall congenital anomaly incidence was 1.11% and the NTD incidence was 0.27% in our population. Anencephaly was the second most common NTDs with the ratio of 40%, following the spina bifida cases. There was a significant difference between female and male newborns with ancephalocele (P < 0.05). Urogenital system anomalies were found to be the second most common type of malformation with an incidence of 0.21%. Facial and musculoskeletal system abnormalities were the third and fourth most common malformations. Omphalocele incidence in our population was 5 in 9160 births and gastrochisis was 1 in 9160 births. Conclusion: The overall congenital anomaly incidence in newborns in our population is 1.11%. The most common malformations were CNS and urogenital abnormalities. NTDs incidence was 0.27% in a Turkish population.

Factors affecting live birth rate in intrauterine insemination cycles with recombinant gonadotrophin stimulation

The objective of this cross-sectional study was to identify the prognostic factors that influence the outcome of ovarian stimulation with intrauterine insemination (IUI) cycles using gonadotrophins in couples with unexplained and mild male-factor subfertility. A total of 838 cycles in 456 women with unexplained and mild male-factor subfertility attending a university-based infertility clinic was evaluated. Of these cycles, 139 resulted in pregnancy (16.6% per cycle) and 96 out of 98 ongoing pregnancies resulted in live term birth. Live birth rate per patient and per cycle was 21.1% and 11.4%, respectively. Multivariate logistic regression analysis demonstrated that duration of infertility (P = 0.034), type of infertility (P = 0.003), aetiology of infertility (P = 0.004), number of treatment cycles (P = 0.0001) and number of dominant follicles before human chorionic gonadotrophin (HCG; P = 0.024) were significant independent factors to predict clinical pregnancy. The duration of infertility (P = 0.043), number of treatment cycles (P = 0.0001) and number of dominant follicles before HCG (P = 0.024) were significant independent factors to predict live birth. In conclusion, for subfertile couples having shorter duration of subfertility, multifollicular response to gonadotrophins and in their first treatment cycle are more likely to succeed a live birth with IUI treatment using recombinant gonadotrophins.

Poor ovarian response in women undergoing in vitro fertilization is associated with altered microRNA expression in cumulus cells

OBJECTIVE To analyze the association of micro-ribonucleic acid (miRNA) expression with the number of oocytes retrieved, in women undergoing in vitro fertilization (IVF). DESIGN Experimental study. SETTING Academic medical center. PATIENT(S) A total of 189 women undergoing IVF-intracytoplasmic sperm injection (ICSI). INTERVENTION(S) Pooled cumulus cells were collected. MAIN OUTCOME MEASURE(S) Poor responders were identified as patients who produced fewer oocytes than the 25th percentile of their respective age group. MicroRNAs were extracted from cumulus cells, and an miRNA microarray was performed, comparing poor responders (n = 3) to non-poor responders (n = 3). Expression of miR-21-5p (active strand of miR-21) and miR-21-3p was tested in poor responders (n = 21) and non-poor responders (n = 29), using reverse transcription real-time polymerase chain reaction (qRT-PCR). Regulation of miR-21-5p and miR-21-3p, in human granulosa-like tumor (KGN) cells, by estradiol (E2), was tested in vitro. RESULT(S) MicroRNA microarray analysis showed up-regulation of 16 miRNAs and down-regulation of 88 miRNAs in poor responders. Notably, miR-21 was significantly up-regulated 5-fold in poor-responder samples. Analysis using qRT-PCR confirmed that miR-21-5p expression was significantly up-regulated in poor responders, whereas miR-21-3p expression was significantly lower, suggesting that elevated miR-21-5p expression in cumulus cells is not regulated at the pre-miR-21 level in poor responders. Both miR-21-5p and miR-21-3p were increased in KGN cells in response to higher doses of E2; their expression was not affected at lower E2 concentrations. CONCLUSION(S) We found that poor response to IVF is associated with altered miRNA expression in cumulus cells, specifically with elevated expression of miR-21-5p, and that this elevated expression is independent of lower serum E2 levels in poor responders.

A potential novel treatment strategy: inhibition of angiogenesis and inflammation by resveratrol for regression of endometriosis in an experimental rat model

Abstract The aim of our study was to evaluate the effectiveness of resveratrol in experimentally induced endometrial implants in rats through inhibiting angiogenesis and inflammation. Endometrial implants were surgically induced in 24 female Wistar–Albino rats in the first surgery. After confirmation of endometriotic foci in the second surgery, the rats were divided into resveratrol (seven rats), leuprolide acetate (eight rats), and control (seven rats) groups and medicated for 21 d. In the third surgery, the measurements of mean areas and histopathological analysis of endometriotic lesions, VEGF, and MCP-1 measurements in blood and peritoneal fluid samples, and immunohistochemical staining were evaluated. After treatment, significant reductions in mean areas of implants (p < 0.01) and decreased mean histopathological scores of the implants (p < 0.05), mean VEGF-staining scores of endometriotic implants (p = 0.01), and peritoneal fluid levels of VEGF and MCP-1 (p < 0.01, for VEGF and p < 0.01, for MCP-1) were found in the resveratrol and leuprolide acetate groups. Serum VEGF (p = 0.05) and MCP-1 (p = 0.01) levels after treatment were also significantly lower in the resveratrol and leuprolide acetate groups. Resveratrol appears to be a potential novel therapeutic agent in the treatment of endometriosis through inhibiting angiogenesis and inflammation. Further studies are needed to determine the optimum effective dose in humans and to evaluate other effects on reproductive physiology.

Contraceptive practices of women after abortion in Turkey

Objectives The aim of this study was to determine the postabortion contraception choices of women and the subsequent reduction in pregnancy rate. The changes in method of contraception during the 1-year follow-up period were also assessed. Methods Ninety women decided to practice family planning methods following an abortion procedure. The family planning choices of the postabortion family planning group were determined by active immediate family planning counselling. The control group, which consisted of 23 women who had had an abortion and wanted to become pregnant again, were followed-up for 1 year to determine their pregnancy rate. The pregnancy rates and methods used were determined during a 12-month follow-up period. Results Following counselling, 79.64% of the patients signed for immediate family planning practice. In the postabortion family planning group, one out of 90 patients (1.1%, Pearl index 1.29) practising contraception with a condom became pregnant. However, ten out of 23 (43.5%, Pearl index 54.2) patients in the control group became pregnant during the 1-year follow-up period (p < 0.05). In the postabortion family planning group, intrauterine devices (IUDs) (n = 43), injectable monthly contraceptives (n = 24) and tubal ligation (n = 9) were the most commonly preferred methods, with 47%, 27% and 10% of the women using these methods, respectively. At the end of the 12-month period, the drop-out rate among women using the injectable monthly contraceptives was significantly higher (13 patients, 54%) compared to other methods (p < 0.05). In one case out of 43 using an IUD (2.38%), the IUD was expelled during follow-up. Conclusion The use of postabortion family planning significantly decreased the postabortion pregnancy rate. The use of an IUD was the preferred immediate method of choice. Use of injectable monthly contraceptives was the method with the highest drop-out rate. The expulsion rate of postabortion IUDs was acceptable in our practice. The pregnancy rate in the control group was lower than the physiological fecundity would predict. This may suggest that, although couples plan to get pregnant, they do not concentrate on the ideal conditions for conception or they do, in fact, practice some form of family planning.

Influence of exogenous estrogen administration on serum CA-125 originating from the endometrium

Objectives: The purpose of the study is to assess the endometrial contribution of serum CA‐125 using exogenous estrogen administration by ruling out ovarian activity. A randomized, controlled, prospective study was designed to assess the endometrial contribution of serum CA‐125 and its influence from estrogen administration in menopausal women. Methods: Twenty menopausal women with intact uterus and ovaries (study group) and 10 cases with previous total hysterectomy with intact ovaries (control group) were included in the study. The mean age of subjects in the study and control groups were similar at 53±1.9 (S.D.) and 51±2.7 years. The length of menopause in the study and control groups were also similar at 61.0±18 and 52.6±26.5 months, respectively. Group 1 consisted of 10 randomly selected cases and five controls who received 15 days of 50 μg/day transdermal 17β‐estradiol (TE). Group 2 consisted of the next randomly selected 10 cases and five controls who had 15 days of transdermal 100 μg/day 17β‐estradiol (Estraderm‐Ciba) administration. Serum CA‐125 and estradiol were measured at day 0, 15 by radioimmunoassay (RIA). Results: Serum mean CA‐125 levels increased significantly in endometrium intact menopausal women from day 0 to 15 of TE administration in group 2 and 1, 70% and 6%, respectively (P=0.03 and P=0.05, respectively). Interestingly, the increase in serum estradiol levels accompanied this change only in group 2. Conclusions: These results suggest that endometrial CA‐125 secretion to serum is dependent on the dose of administered exogenous estrogen.

The effects of 3-day clomiphene citrate treatment on endocrine and ovulatory responses

A prospective cohort, paired clinical trial was carried out to test a shorter clomiphene citrate regimen of 3 days, measuring the endocrine outcomes and ovulatory responses. The trial took place at Gazi University Medical School Department of Obstetrics and Gynecology. The 28 infertile patients were newly accepted to the clinic with hypothalamopituitary disorder according to WHO classification Group II. They were treated with 50 mg/day clomiphene citrate (CC) for 3 days in 63 cycles. The control group of 28 paired patients were treated with 50 mg/day CC for 5 days in 40 cycles. The main outcome measures were: serum estradiol levels on day 11 (E-11), 14 (E-14) and postovulatory day 7 (E+ 7); serum progesterone levels on postovulatory day 7 (P+ 7); endometrial thickness on day 14 of the cycle; mean follicular phase length; and ovulation rates. The mean ages, gravidas, paritas, menstrual histories, E-11, P+ 7 levels, mean follicular phase length and luteal phase length were similar in both groups. E-14 (229.76 +/- 156.05 pg/ml vs. 338.25 +/- 350.60 pg/ml) and E+ 7 (217.30 +/- 114.95 pg/ml vs. 310.6 +/- 11.05 pg/ml) were significantly lower, whereas mean endometrial thickness on day 14 (10.30 +/- 1.39 mm vs. 9.52 +/- 1.96 mm) were significantly higher in the study group compared to controls (p < 0.05). Ovulation occurred in 82.53% of cycles in the study group and 95% in controls. In the study group, pregnancy was achieved in 17.3% of the ovulatory cycles; this rate was 10.5% in the control group. To decrease the peripheral antiestrogenic effects of CC, a regimen of 50 mg/day for 3 days may be used as a starting dose instead of the standard 5-day regimen.

Infertility and surrogacy first mentioned on a 4000-year-old Assyrian clay tablet of marriage contract in Turkey

Abstract Mankind has been expressing the breeding topic for thousands of years. Reproduction is the primary instinct of human beings and it is a social, cultural, medical issue. Demographic infertility is one of them, which is defined infertility as the inability to become pregnant with a live birth, within five years of regular sexual contact based upon a consistent union status in marriage maintaining a desire for a child with the lack of contraceptive use and non-lactating. A first mentions about infertility and surrogacy is discovered on a 4000-year-old clay tablet of marriage contract belonging to the Assyrian period exhibited at Istanbul Archeology Museum in Turkey. In conclusion, there are many different ways to solve infertility problems like surrogacy as mentioned even 4000 years ago in this Assyrian clay tablet of marriage contract as the first time in the literature. Medical treatments in relation to human infertility will continue to be the focus of social and cultural debates. Hence, more legislation and regulation will come in many countries to control the unauthorized exploitation of the patient.

The effect of captopril on endometriotic implants in a rat model

OBJECTIVE To determine the effects of captopril on experimentally induced endometriosis in a rat model. STUDY DESIGN Twenty-four adult, mature female Wistar-Albino rats in which endometriotic implants were induced by transplanting autologous uterine tissue to ectopic sites on the peritoneum. After the endometriotic implants were formed surgically, the 24 rats were randomly divided into three groups. Group 1 (captopril group, eight rats) were given 50 mg kg(-1)d(-1) of oral captopril for 21 d. Group 2 (leuprolide acetate group, eight rats) were given a single 1 mg kg(-1) subcutaneous injection of leuprolide acetate. Group 3 (control) were given no medication and served as controls (eight rats). The surface area of the endometriotic implants and the score of histologic analysis. Also, VEGF and MCP-1 levels in peritoneal fluids and bloods were analyzed. RESULTS At the beginning of the medical treatment, the mean surface areas of the endometriotic implants were comparable in all three groups. At the end of the treatment the mean implant surface area in the captopril group and leuprolide acetate group was less than that in the control group. Mean histopathological examination score for the implants post treatment was lower in the captopril and leuprolide acetate groups. Peritoneal fluids VEGF level in the captopril and leuprolide acetate groups was lower than that in the control group. The post-treatment MCP-1 level was also lower in the captopril and leuprolide acetate groups than in the control group. The serum VEGF and MCP-1 levels post treatment were significantly lower in the captopril and leuprolide acetate groups than in the control group. CONCLUSION Administration of captopril reduced the size and progression of endometriotic lesions in a rat model.