International Journal of Fertility and Sterility

257-270

Authors: Moustafa A. Gadalla, Robert J. Norman, Chau T Tay, Danielle S. Hiam, Angela Melder, Jyotsna Pundir, Shakila Thangaratinam, Helena J Teede, Ben W.J. Mol, Lisa J. Moran

Polycystic ovary syndrome (PCOS) is a common, complex condition that affects up to 18% of reproductive- aged women, causing reproductive, metabolic and psychological dysfunctions. We performed an overview and appraisal of methodological quality of systematic reviews that assessed medical and surgical treatments for reproductive outcomes in women with PCOS. Databases (MEDLINE, EMBASE, CINAHL PLUS and PROSPERO) were searched on the 15th of September 2017. We included any systematic review that assessed the effect of medical or surgical management of PCOS on reproductive, pregnancy and neonatal outcomes. Eligibility assessment, data extraction and quality assessment by the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool were performed in duplicate. We identified 53 reviews comprising 44 reviews included in this overview; the majority were moderate to high quality. In unselected women with PCOS, letrozole was associated with a higher live birth rate than clomiphene citrate (CC), while CC was better than metformin or placebo. In women with CC-resistant PCOS, gonadotrophins were associated with a higher live birth rate than CC plus metformin, which was better than laparoscopic ovarian drilling (LOD). LOD was associated with lower multiple pregnancy rates than other medical treatments. In women with PCOS undergo- ing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), the addition of metformin to gonadotro- phins resulted in less ovarian hyperstimulation syndrome (OHSS), and higher pregnancy and live birth rates than gonadotrophins alone. Gonadotrophin releasing hormone (GnRH) antagonist was associated with less OHSS, gonadotrophin units and shorter stimulation length than GnRH agonist. Letrozole appears to be a good first line treatment and gonadotrophins, as a second line treatment, for anovulatory women with PCOS. LOD results in lower multiple pregnancy rates. However, due to the heterogeneous nature of the included popula- tions of women with PCOS, further larger scale trials are needed with more precise assessment of treatments according to heterogeneous variants of PCOS.

277-281

Authors: Elham Amirchaghmaghi, Farideh Malekzadeh, Mohammad Chehrazi, Zahra Ezabadi, Shokufeh Sabeti

Background It is thought that mothers who conceive via assisted reproductive technology (ART) may be at greater risk of postpartum depression (PPD) because of the problems and psychological stresses associated with ART treat- ment. The aim of the present study is to determine the occurrence of PPD among mothers who conceive by ART in comparison with mothers who naturally conceive. The Edinburgh Postnatal Depression Scale (EPDS) was used to assess PPD. Materials and Methods This historical cohort study investigated 406 mothers with infants aged 3-9 months. Three hundred and eight women with natural pregnancies were selected as the control group from mothers who referred to Tehran healthcare centres for infant vaccinations. The ART group consisted of 98 women who conceived via ART at Royan Institute. Participants completed a general questionnaire that asked about education, occupation, number of children, delivery method, history of infant hospitalization, breastfeeding, mothers’ and infants’ ages, cause of infertil- ity (ART group), and history of depression. A validated Persian version of the EPDS was used to measure depressive symptoms. Results The mean EPDS score in mothers who naturally conceived was 8.38 ± 0.35 in comparison with mothers who conceived via ART (7.59 ± 0.63). The proportions of women who reported PPD were 26.0% for the control group and 20.4% for the ART group. There was no statistically significant difference in PPD between the control and ART groups (P=0.26). Conclusion The occurrence of PPD in mothers who conceived via ART was similar to those who conceived naturally.

289-295

Authors: Ashraf Moini, Fatemeh Zafarani, Nadia Jahangiri, Shahideh Jahanian Sadatmahalleh, Maria Sadeghi, Mohammad Chehrazi, Firoozeh Ahmadi

Background The aim of this study was to investigate the effects of vaginal sildenafil on the outcome of patients with at least two unsuccessful in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) attempts. Materials and Methods In this randomized placebo-controlled trial study, a total of 66 infertile women aged ≤38 years, with a history of normal ovarian reserve, two prior consecutive failed IVF/ICSI attempts, human chorionic gonadotropin (hCG) day endometrial thickness <7 mm in all prior IVF/ICSI cycles, normal endometrial appear- ance by either hysteroscopy, hysterosonography, or hysterosalpingography enrolled in this study. The conventional gonadotropin-releasing hormone (GnRH) protocol was used for ovarian stimulation. The patients were randomly divided into three groups: vaginal sildenafil (suppository-100 mg/daily), vaginal placebo/sildenafil (suppository-100 mg/daily), and vaginal placebo (suppository). Each patient underwent colour Doppler ultrasound on day 14 of their previous cycle to investigate any abnormalities in the uterus and adnexa. Endometrial thickness, echo pattern, uterine artery resistance, and pulsatility indices were recorded pre- and post-treatment. The primary outcome measures were implantation, chemical and clinical pregnancy rates. For data analysis, SPSS version 20 software was used. In all tests, the significance level was considered less than 0.05. Results There was no significant difference between three groups in endometrial thickness on the hCG injection day. The chemical pregnancy in women who received sildenafil (alone or in combination with placebo) showed a two-fold increase in comparison to the placebo group. This increase was clinically meaningful, but according to sample size, it was statistically non-significant. The results of our study showed that the implantation was higher in women who received placebo/sildenafil compared to the other groups. The abortion rate was not statistically significant among the groups. Conclusion Vaginal sildenafil may conceivably improve chemical pregnancy rates in repeated IVF failure patients. Further randomized clinical trials using oral or vaginal sildenafil with higher sample size are recommended (Registra- tion number: NCT03192709).

301-306

Authors: Samira Rezaei-Mojaz, Zohreh Nazmara, Mohammad Najafi, Mansoureh Movahedin, Zahra Zandieh, Peymaneh Shirinbayan, Mohsen Roshanpajouh, Hamid Reza Asgari, Mehdi Abbasi, Morteza Koruji

Background The aim of this study was to investigate two enkephalin-degrading enzymes, aminopeptidase N (APN/ CD13) and endopeptidase (NEP/CD10), gene and protein expression levels in sperm samples of fertile and heroin- addicted men, and the correlation between their expressions and semen quality. Materials and Methods In this case-controlled study, semen was collected from 24 normozoospermic healthy (as a control group) and 24 heroin-addicted men donors (as case or addiction group). Sperm cells isolated by Cook Medical gradient (40-80%) and followed up by swim-up techniques were used for real-time quantitative polymer- ase chain reaction (qPCR) and flow cytometry techniques to assess APN/CD13 and NEP/CD10 genes and proteins subsequently. Semen parameters were analyzed by computer-assisted sperm analysis. Results The findings revealed that there were significant differences in sperm total motility (41.07 ± 3.63 vs. 63.03 ± 3.31 %, P=0.0001), progressive motility (35.21 ± 2.64 vs. 20.93 ± 3.22%, P=0.001) and viability (69.9 ± 4.69 vs. 86.81 ± 1.26 %, P=0.002) in the addicted group vs. control ones. APN and NEP gene expression levels in the addicted group decreased compared with the control ones (1.00 ± 0.67 vs. 0.36 ± 0.13, P= 0.008 and 1.07 ± 0.11 vs. 0.52 ± 0.12 0.002, respectively). Flow cytometry analysis showed that the average percent of APN/CD13 in heroin consumers significantly decreased compared with the healthy ones, while NEP/CD10 rate between two groups was similar. We also observed that duration of drug dependence is correlated with sperm viability (r=-0.627, P=0.016) and motility (r=-0.410, P=0.05), NEP (r=-0.434, P= 0.049), and APN (r=-0.641, P=0.002) gene expression levels. Conclusion We conclude that semen quality and enkephalin-degrading enzymes were altered in heroin-addicted men. other confirming the internal validity of our estimates.

315-323

Authors: Abdul Razzaq S Alsalman, Lamia A. Almashhedy, Abdulsamie H. Alta'ee, Mahmoud H. Hadwan

Background Uric acid (UA) is crucial for sperm metabolism as it protects seminal plasma against oxidative dam- age. Zinc also plays a central role in sperm metabolism. The current study was designed to investigate the role of zinc supplementation on qualitative and quantitative properties of seminal fluid, in parallel with the UA level and urate pathway enzymes in the semen of patients with asthenozoospermia. Materials and Methods The study was designed as a randomized controlled trial of 60 asthenozoospermic subfertile men. The current study, which was conducted during one year, involved 60 fertile and 60 asthenozoospermic subfertile men belonging to Hilla City, Iraq. Semen samples were obtained from the participants before and after treatment with zinc supplements. The levels of UA, xanthine oxidase (XO), adenosine deaminase (ADA) and 5'-nucleotidase (5'-NU) activities were determined in spermatozoa and seminal plasma of both groups. Results UA levels (P=0.034) and 5'-NU activity (P=0.046) were significantly lower but ADA (P=0.05) and XO (P=0.015) activities were significantly higher in infertile men than in healthy men. Treatment with zinc sulfate induced an increase in UA (P=0.001) level and 5'-NU activity (P=0.001), but a decrease in ADA (P=0.016) and XO (P=0.05) activities. Conclusion Zinc supplementation restores UA levels and the activities of enzymes involved in the urate pathway (XO and ADA) in the seminal plasma and spermatozoa of patients with asthenozoospermia, to reference values. Sup- plementation of Zn compounds enhances the qualitative and quantitative properties of semen (Registration number: NCT03361618).

330-338

Authors: Parisa Jamalzaei, Mojtaba Rezazadeh Valojerdi, Leila Montazeri, Hossein Baharvand

Background In the present study, the effects of alginate (ALG) concentration and ovarian cells (OCs) on the devel- opment and function of follicles were simultaneously evaluated. Materials and Methods In the first step of this experimental study, preantral follicles were isolated from the ovaries of 2-week-old mice, encapsulated in the absence or presence of OCs in 0.5, 0.75 and 1% ALG hydrogels, and cultured for 14 days. The morphology, diameter, survival and antrum formation rates of the follicles and the maturation of the oocytes were evaluated during culture. In the second step, preantral follicles were cultured in the best chosen ALG concentration, in both the absence and presence of OCs. Following these steps, the amount of DNA fragmentation, the expression levels of connexin 37 and connexin 43 proteins, the secretion levels of estradiol, progesterone and andros- tenedione by the follicles and the quality of mature (MII) oocytes were assessed. Results Our data revealed that in the absence of OCs, follicles of 0.5% group showed a higher survival rate than the 0.75 and 1% groups (71.87 vs. 52.52 and 40%, respectively, P<0.05). Nonetheless, the antrum formation rate of the 1% group was higher and its oocyte degeneration rate was lower than that in the other groups. Furthermore, it was observed that co-culture of follicles with OCs relatively increased the follicle diameter, survival, antrum formation, and germinal vesicle (GV) to GV break down (GVBD)/MII transition rates. At last, the comparison of 0.5%-OCs and 0.5%+OCs groups indicated that the co-culture condition resulted in more progesterone production (1.8 ± 0.2 vs. 3.2 ± 0.4 ng/ml, respectively, P<0.05) and also decreased oocytes’ cortical granule abnormalities (100 vs. 40% for 0.5%- OCs and 0.5%+OCs groups, respectively). Conclusion The present study revealed that 0.5% ALG hydrogel is relatively suitable for preantral follicle culture, and in the presence of OCs, it mimics the natural ovarian condition better than the higher concentrations of ALG hydrogel.

346-347

Authors: Abdelmonem Awad Hegazy

The ovarian reserve (OR) gradually decreases throughout the female fertile life. This continuous depletion in OR is irreversible. This occurs through a programmed cell death, known as apoptosis. Some factors hasten such depletion, such as chemo- and radio-therapy. Others have been investigated in trials to preserve the OR including gonadotropins, cytokines, growth hormones, nitric oxide and reorganization of the actin cytoskeleton. Loss of OR occurs normally at the menopausal age, a stage called menopausal ovarian senescence. At some periods, there are other sources for ovarian hormones that are away from the ovary, like during use of contraceptive pills and at pregnancy after formation of placenta. Future trials to preserve ovarian follicles at these periods might postpone the onset of menopause and hence lengthen the fertile female age.