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

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.

Gonadotropin-Releasing Hormone Analog Combined with Depot Medroxyprogesterone Acetate in the Management of Endometrial Hyperplasia A Prospective Randomized Clinical Study.

OBJECTIVE: To compare the effectiveness of combined treatment of depot medroxyprogesterone acetate (MPA) with gonadotropin-releasing hormone (GnRH) analog and depot MPA alone in the management of simple endometrial hyperplasia without atypia among heavy bleeders. STUDY DESIGN: Thirty- four patients with endo- metrial hyperplasia with- out atypia were selected in this prospective randomized study. Group I consisted of 15 patients who were treated with depot MPA combined with GnRH analog. Group 2 consisted of 19 patients who were treated with depot MPA alone. Injections were applied at the beginning of the study and at the end of the 3rd month. Endometrial biopsies were performed at the end of the 6th month. Main outcome measures were endometrial response and reduction of duration and amount of menstrual bleeding. RESULTS: Total and mean duration of menstruation and total number of standardized pads used were signifi- cantly decreased in both groups. These parameters were also significantly lower in group 1 than in group 2 at the end of both the 3rd and 6th months of the study (p<0.01). Endometrial response rates were significant- ly higher in group I than in group 2 (100% vs. 44.4%, respectively, p <0.05). CONCLUSION: Management of endometrial hyper- plasia with GnRH analog in addition to depot MPA provides prompt endometrial response and rapid menstru- al cycle control.

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

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.

The Effect of Prednisolone Treatment on Pregnancy Rates in in vitro Fertilization Patients with Positive Thyroid Autoantibodies.

OBJECTIVE: This study aims to investigate the effect of prednisolone treatment on the pregnancy rates of in vitro fertilization (IVF) patients with positive thyroid autoantibodies. METHODS: This study was conducted in the IVF unit of Gazi University Faculty of Medicine. It included 158 patients who underwent intracytoplasmic sperm injection using the long-term protocol of a gonadotropin-releasing hormone (GnRH) agonist that was positive for thyroid autoantibodies. Each test's reference value was used as a positive measure of anti-thyroid peroxidase and anti-TG antibodies. On the day of oocyte intake, 44 of 158 patients were started on prednisolone, and the other 114 patients were followed up without medication. RESULTS: In the control group, pregnancy did not occur in 67.5% of the patients; it was determined that 21.1% were pregnant, 5.3% had biochemical pregnancies, 4.4% had twin pregnancies, 0.9% had triplet pregnancies, and 0.9% had ectopic pregnancies. In the extended prednisolone group, pregnancy did not occur in 56.8% of the patients; it was determined that 36.4% of them were pregnant, 4.5% had twin pregnancies, and 2.3% had biochemical pregnancies. An increase in pregnancy rate was observed in the extended prednisolone group, while a statistically significant difference was found between the groups in terms of the mean values of prednisolone according to pregnancy status (p<0.05). It was thus determined that the rate of conception increased in the extended prednisolone group compared to the controls. CONCLUSION: There is a strong relationship between the presence of thyroid autoantibodies and poor IVF results. The coadministration of prednisolone can improve the clinical pregnancy rate in women affected by thyroid autoimmunity.

A cross-sectional study in non-anaemic pregnant women in Turkey to assess necessity of iron supplementation.

BACKGROUND: Iron deficiency is the most common cause of anaemia in pregnancy. Guidelines recommend different threshold values for iron supplementation. AIMS: To determine trimester-specific reference ranges for haematological values (haemoglobin, hematocrit and ferritin) in healthy pregnant women who have not used any iron supplementation during pregnancy to guide future iron treatment. METHODS: A prospective cross-sectional study was carried out on 168 pregnant women aged 18-45 years, with singleton pregnancies in the first trimester, Hb ≥ 11 g/dL and ferritin ≥ 12 µg/L, and not using iron supplementation. Multiple pregnancies, pregnancies with obstetric complications and smokers were excluded from the study. Mean haemoglobin (Hb) and ferritin values, trimester-specific reference ranges and percentile values of Hb and ferritin were determined for each trimester. The normality of the variables was tested using the Kolmogorov-Smirnov test. RESULTS: Mean Hb decreased significantly between trimesters from 12.6 to 11.9 and then 11.5 g/dL. In addition, Hb, hematocrit and ferritin decreased significantly from the first to the second trimester (P < 0.001 for all) but stayed comparable between the second and third trimesters (P = 0.246, P = 0.575, P = 0.408, respectively). The lower reference value for Hb was calculated as 10.67, 10.08 and 9.18 g/dL for 10-14, 20-24 and 30-34 gestational weeks respectively. CONCLUSION: This pioneer study allows us to understand that iron supplementation may not be needed as any decrease is due to physiological haemodilution. These results may prevent unnecessary iron prescription during pregnancy.

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.

Women with and without menopause over age of 40 in Turkey: consequences and treatment options.

AIM: To investigate the characteristics of menopausal population who gets free first step health-care services from government facilities in the Central Anatolia Region of Turkey. METHODS: One thousand and forty-nine pre- (N = 403) and post (N = 646)-menopausal females were interviewed with a questionnaire in five different facilities during 2 weeks. RESULTS: The group, who never used oral contraceptive as a family planning method, never smoked and had a low rate of illiteracy (72.5, 72.5, 77.7, and 12.1%, respectively. Mean age of the menopause was 45.8 +/- 5.5 years. Mean years since menopause was 13.2 +/- 9.6 years and mode of the menopause was 10 years. Group of postmenopausal women knew the meaning of menopause as "ceasing of menses" in a significantly higher rate compared to pre-menopausal group (6.9% versus 2.2%, respectively). While rate of the women regularly visiting free health-care facilities and rate of receiving some form of HRT is observed to be relatively low (33 and 29.4%, respectively), no significant differences were observed in symptoms rating between pre- and post-menopausal group restlessness, uneasy feeling, insomnia, flushing, sweating, tachycardia, short memory, bone and muscle pain, and nocturia and therefore such symptoms seem to be unrelated to their menopausal status. CONCLUSIONS: Women are entering to menopause earlier and using the free medical facilities in this region of Turkey less, compared to European population and seeking less help for menopause during this period. They are mostly married, with lower preferences for oral medications, non-smokers, relatively literate group of people; however, with low awareness of their current situation regarding the phenomenon of "ceasing of menses" and its consequences.

Comparison of The Effectiveness of Clomiphene Citrate versus Letrozole in Mild IVF in Poor Prognosis Subfertile Women with Failed IVF Cycles.

BACKGROUND: Our objective was to evaluate the effectiveness of clomiphene citrate (CC) vs. letrozole (L) plus human menopausal gonadotropin (hMG) in gonadotropin releasing hormone (GnRH) antagonist protocol in poor prognosis women with previous failed ovarian stimulation undergoing intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: This retrospective cohort study included cycles with CC and L plus hMG/GnRH antagonist protocols of 32 poor responders who had failed to have ideal follicles to be retrieved during oocyte pick-up (OPU) or embryo transfer (ET) at least for 2 previous in vitro fertilization (IVF) cycles with microdose flare protocol or GnRH antagonist protocol from January 2006 to December 2009. Main outcome measures were implantation, clinical pregnancy and live birth rates per cycle. Duration of stimulation, mean gonadotropin dose used, endometrial thickness, number of mature follicles, serum estradiol (E2) and progesterone (P) levels on the day of human chorionic gonadotropin (hCG) administration, number of retrieved oocytes and fertilization rates were also evaluated. RESULTS: A total number of 42 cycles of 32 severe poor responders were evaluated. Total gonadotropin consumption was significantly lower (1491 ± 873 vs. 2808 ± 1581 IU, P=0.005) and mean E2 level on the day of hCG injection were significantly higher in CC group than L group (443.3 ± 255.2 vs. 255.4 ± 285.2 pg/mL, P=0.03). ET, overall pregnancy and live birth rates per cycle were significantly higher in CC than L protocol (27.2 vs. 15%, 13.6 vs. 0% and 4.5 vs. 0%, respectively, P<0.05). CONCLUSION: Severe poor responders who had previously failed to respond to microdose or GnRH antagonist protocols may benefit from CC plus hMG/GnRH antagonist protocol despite high cancellation rate.

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.

Autoimmune progesterone dermatitis.

Autoimmune progesterone dermatitis (APD) is an uncommon cutaneous disorder characterized by exacerbations during the luteal phase of the menstrual cycle. We describe a 27-year-old woman with a recurrent skin eruption for 3 years. She had no history of exposure to synthetic progesterones. At each menses, the patient developed scaly, erythematous maculopapular lesions over the face. Intradermal skin test reaction to progesterone was positive. Progesterone sensitivity was also demonstrated by challenge test with intramuscular progesterone acetate. These features were consistent with the diagnosis of APD. Our patient was treated successfully with conjugated estrogen for 6 months. At one year follow-up, the patient had had no recurrence of facial eruption.

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.

Gonadotropin-releasing hormone analog combined with a low-dose oral contraceptive to treat heavy menstrual bleeding.

OBJECTIVE: To compare the effects of low-dose oral contraceptives used alone and in combination with a gonadotropin-releasing hormone (GnRH) analog to treat heavy menstrual bleeding. METHODS: Fifty-eight patients with heavy menstrual bleeding were prospectively randomized into two treatment groups to receive either a low-dose oral contraceptive alone (group 1), or combined with a GnRH analog (group 2) for 6 months. The patients' hormonal profiles, and hemoglobin and hematocrit levels were measured at the beginning and at the end of the treatment period. RESULTS: Hemoglobin and hematocrit levels significantly improved in both groups after 6 months of treatment (P<0.05 and P<0.01, respectively). Even in the first month of the study, the number of pads used and the duration of menstruation were significantly decreased in both groups and markedly lower in group 2 (P<0.01). CONCLUSION: The addition of a GnRH analog to low-dose oral contraceptive treatment for heavy menstrual bleeding resulted in better control of vaginal bleeding, even in the first month of therapy.