International Journal Of Fertility and Sterility
Volume:13 Issue: 1, April-June 2019

Urocortin (UCN) is a neuropeptide that belongs to the corticotrophin-releasing hormone family and is expressed by eutopic and ectopic human endometria. The past years, this expression has been thoroughly investigated in the field of endometriosis. The objective of this systematic review is to accumulate current evidence related to the expression of UCN in tissue and blood samples of patients suffering from endometriosis. Literature search was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and primarily conducted using the Medline (1966-2018), Scopus (2004-2018), EMBASE (1947-2018) and Clinicaltrials.gov (2008- 2018) databases, along with the reference lists of electronically retrieved full-text papers. Overall, eight studies were retrieved. Current evidence suggests that the expression of UCN is increased in patients with ovarian endometriomas and that its levels may correlate with the severity of the disease. The diagnostic efficacy of UCN1 plasma levels was evaluated in three studies. Two of them suggested that the sensitivity and specificity of the method may reach, and even exceed, 80%. However, the wide variation in outcome reporting and outcome reporting measures in endometriosis among the included studies precludes meta-analysis of available data. Therefore, although UCN seems to be a promising biomarker for the identification and follow-up of patients that suffer from endometriosis, more studies are needed to reach firm conclusions with respect to its predictive accuracy.

Tumor necrosis factor-alpha (TNF-α) is an important cytokine in acute inflammatory response to infective factors. Based on investigation in different populations, it is thought that this response increases in patients with endometrio- sis due to the presence of cytokines such as TNF-α. This study aimed to examine the association of four TNF-α polymor- phisms, namely -238G/A, -308G/A, -857C/T and -863C/A, with susceptibility to endometriosis in an Iranian population. We recruited 150 women with endometriosis and 150 women without endometriosis in this case-control study and collected 4 ml of blood from all subjects. After DNA extraction, the polymorphisms were geno- typed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The allele frequency of TNF-α -863C/A in the case and control groups showed a significant difference [odds ratios (OR)=0.64, 95% confidence interval (CI)=0.41-0.99, P=0.047] but the result is not significant when Adjust- ing for multiple testing (P=0.188). No significant difference in the allele frequencies of -238G/A (OR=1.07, 95% CI=0.51-2.25, P=0.862), -308G/A (OR=0.79, 95% CI=0.43-1.45, P=0.438) and -857C/T (OR=1.03, 95% CI=0.66- 1.61, P=0.887) was observed. We adjusted all four polymorphism genotypes by age and body mass index (BMI), however, no significant difference was detected. There was an association between the case and control and BMI when adjusting by age (OR=1.082, 95% CI=1.009-1.162, P=0.028). For the first time the association of the four polymorphisms in the promoter region of the TNF-α gene with endometriosis has been conducted in women of Iranian origin. The present research reveals the -863 A allele may play a role in incidence of endometriosis among Iranian women. Development of endometriosis among those people with -863 A allele seems low. According to the results, the current study indicates that there might be a correlation between BMI and progression of endometriosis.

The prognostic value of peripheral natural killer (pNK) cells, as a screening test in women with recur- rent pregnancy loss (RPL) and unexplained infertility, is still a matter for discussion. The purpose of this study was to compare the percentage of circulating CD56+NK cells, CD69 and perforin markers between women with unexplained infertility and RPL with the healthy control group. In this case-control study, the percentage of CD56+NK cells and activation markers (CD69 and perforin levels) in the peripheral blood were measured in 25 women with unexplained infertility, 24 women with idiopathic RPL and 26 women from the healthy control group, using specific monoclonal antibodies by flow cytometry. The percentage of CD56+NK cells was significantly higher in patients with infertility in comparison with the healthy control group (P=0.007). There were not significant differences either in the total number of CD56+cells between the RPL group and the control group (P=0.2) or between the RPL group and the infertile group (P=0.36). The percentage of CD69+lymphocytes in RPL group was significantly higher than in the infertility group (P=0.004). There was a statistically significant difference in Perforin levels between RLP and control (P=0.001) as well as RPL and infertile (P=0.002) groups. An increased percentage of CD56+NK cells in patients with unexplained infertility, an elevated expression of CD69 on NK cells in patients with RPL and infertility and a high level of perforin on CD56+cells in the RPL group might be considered as immunological risk factors in these women.

Despite numerous studies indicating an imperative role for reproduction, however, the role of Vitamin D supplementation on outcomes of assisted reproductive techniques remains controversial. This clinical trial was per- formed to evaluate the effect of Vitamin D supplementation 6 weeks prior to intracytoplasmic sperm injection (ICSI) on fertility indices. The present study was a double-blind clinical trial conducted on infertile women was ran- domly allocated into two groups: Vitamin D supplementation (42 participants) and placebo (43 participants). Serum Vitamin D was measured before and six to eight weeks after treatment, on the day of ovum pick up. Results were analyzed using SPSS16 and fertility indices were compared between the two groups. No significant difference was observed between the intervention and control groups regarding the mean number of oocytes retrieved, percentage mature oocyte, fertilization rate and the rate of good quality embryos (all P>0.05). But, percentages of the individual with suitable endometrium (7-14 mm thickness) were significantly higher in the Vitamin D compared to control group (P=0.011). The rate of chemical (47.6 vs. 25.5%, P=0.013) and clinical pregnancy rate (38.1 vs. 20.9%, P=0.019) were also significantly higher in the Vitamin D compared to control group. The present study reveals that consuming Vitamin D for 6 weeks prior to ICSI improves quality of endo- metrium, rate of chemical and clinical pregnancy (Registration Number: IRCT2015111124999N1).

We designed the present study to evaluate the simultaneous effect of obesity in couples on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes. In this cross-sectional study, performed at Royan Institute between January 2013 and Janu- ary 2014, we evaluated the recorded data of all patients during this time period. The study population was limited to couples who underwent ICSI or IVF/ICSI cycles with autologous oocytes and fresh embryo transfers. We recorded the heights and weights of both genders and divided them into groups according to body mass index (BMI). Multilevel logistic regression analysis was used to determine the odds ratio for live births following ICSI or IVF/ICSI. In total, 990 couples underwent IVF/ICSI cycles during the study period. Among the ovulatory women, a significant difference existed between the BMI groups. There was a 60% decrease [95% confidence interval (CI): 0.11-0.83] in the odds of a live birth among overweight subjects and 84% (95% CI: 0.02-0.99) decrease among obese subjects. Among the anovulatory women, the association between the BMI and live births presented no clear tenden- cies. We did not observe any significant relationship between male BMI and live birth rate. The results demonstrated no significant association between the couples’ BMI and live birth rate. Based on the present findings, increased female BMI independently and negatively influenced birth rates after ICSI. However, increased male BMI had no impact on live births after ICSI, either alone or combined with in- creased female BMI.

The aim of the present study was to determine the maternal pre-pregnancy body mass index (BMI), first-trimester fasting blood sugar (FBS), and the combination of (BMI+FBS) cut-points for at-risk pregnant women conceived by assisted reproductive technology (ART) to better predict the risk of developing gestational diabetes mel- litus (GDM) in infertile women. In this nested case-control study, 270 singleton pregnant women consisted of 135 (GDM) and 135 (non-GDM) who conceived using ART were assessed. The diagnosis of GDM was confirmed by a one-step glucose tolerance test (O-GTT) using 75 g oral glucose. BMI was classified base on World Health Organization (WHO) criteria. The relationship between BMI, FBS, and BMI+FBS with the risk of GDM development was deter- mined by logistic regression and adjusted for confounding factors. Receiver operating characteristic (ROC) curve analysis was performed to assess the value of BMI, FBS, and BMI+FBS for the prediction of GDM. The GDM group had significantly higher age, BMI, family history of diabetes, and history of polycystic ovary syn- drome in comparison with the non-GDM group (P<0.05). Overweight and obese women had 3.27, and 5.14 folds increase in the odds of developing GDM, respectively. There was a 17% increase in the risk of developing GDM with each 1 mg/dl increase in fasting glucose level. The cut points for FBS 84.5 mg/dl (72.9% sensitivity, 74.4% specificity), BMI 25.4 kg/m2 (68.9% sensitivity, 62.8% specificity), and BMI+FBS 111.2 (70.7% sensitivity, 80.6% specificity) was determined. The early screening and high-quality prenatal care should be recommended upon the co-occurrence of high FBS (≥84.5 mg/dl) in the first-trimester of the pregnancy and the BMI (≥25.4 kg/m2) in pre-pregnancy period in women undergone ART. The combination of BMI and FBS is considered a better prediction value.

In vitro maturation (IVM) is an artificial reproductive technology in which immature oocytes are harvested from the ovaries and subsequently will be matured in vitro. IVM does not require ovarian hyperstimulation (OH) and thus the risk of ovarian hyperstimulation syndrome (OHSS) is avoided. In this study, we assessed the live birth rate per initiated IVM cycle in women eligible for in vitro fertilization/intracytoplasmic sperm injection (IVF/ ICSI) and at risk for OHSS. Furthermore, we followed women who were not pregnant after IVM and committed to a conventional IVF/ICSI procedure. In this multicenter prospective cohort study, we started 76 IVM cycles using recombinant follicle stimulating hormone (rFSH) priming in 68 patients. There were 66 oocyte retrievals, in which a total of 628 oocytes were collected. We incubated the immature oocytes for 24-48 hours and fertilized those that reached metaphase II by ICSI. Three hundred eighty six (61% oocytes) achieved metaphase II. The fertilization rate was 55%. We performed 59 embryo transfers (1.9 embryos per transfer) in 56 women, including 3 frozen embryo transfers. There were four ongoing pregnancies (5.3% per initiated cycle) leading to the birth of a healthy child at term. None of the patients developed OHSS. The ongoing pregnancy rate of the first conventional IVF/ICSI cycle after an unsuccessful IVM cycle was 44%, which was unexpectedly high. We concluded that IVM led to live births but with low effectiveness in our study. Earlier reported IVM success rates are higher which can be caused by a more extended experience in these centers with the intricate laboratory process. However, a possible selection bias in these studies cannot be ruled out. Furthermore, IVM might have a beneficial effect on further IVF/ICSI treatments due to its “ovarian drilling” effect.

The purpose of this study was to compare the effects of Glycyrrhiza glabra (Licorice), a cyclooxyge- nase-2 inhibitor (Celecoxib) and a gonadotropin-releasing hormone analog (Diphereline®), with a control group on endometrial implants in rats. In this experimental study, endometriosis was induced in rats by auto transplantation and after confirmation, the rats were divided into 4 groups that were treated for 6 weeks with normal saline (0.5 ml/day, orally), licorice extract (3000 mg/kg/day, orally), celecoxib (50 mg/kg, twice a day, orally) or diphereline (3 mg/kg, intramuscularly). At the end of treatments, the mean area, volume, histopathology and hemosiderin-laden macrophage (HLM) counts of the endometrial implants were evaluated and compared among the four groups. The mean area, volume and HLM counts of the implants in the licorice group were significantly lower than those of the control group (P<0.001). The histopathologic grades of endometrial implants were significantly decreased by licorice compared to the control group (P<0.001). There was no significant change in the mentioned parameters in rats treated with celecoxib compared to the control group. Diphereline was the most potent agent for suppressing the growth of endometrial implants in terms of all of the above-mentioned parameters. Licorice decreased the growth and histopathologic grades of auto-transplanted endometrial implants. However, while celcoxib had no significant effect, diphereline showed the highest potency for decreasing the endome- trial growth. Licorice may have the potential to be used as an alternative medication for the treatment of endometriosis.

Chlorpyrifos (CPF), an organophosphate pesticide, is widely used in farms in order to preserve crops and fruits. Previous studies have shown that CPF exposure might cause chronic toxicity in male genital system. The present study investigated the protective effect of N-Acetyl Cysteine (NAC), a potent antioxidant against testicular toxicity of CPF in male mice. In this experimental study, 42 adult male mice were divided into seven groups, CPF low (0.5 mg/kg.b.w) and high (5 mg/kg.b.w) doses groups, NAC group (35 mg/kg.b.w), NAC+CPF 0/5 mg/kg.b.w, NAC+CPF 5 mg/kg.b.w, dimethyl sulfoxide (DMSO, 0.75% solution mg/kg.b.w) and control group. All treatment were done intraperitoneally. Treatment was conducted for four consecutive weeks (five days each week). However NAC was injected to NAC+CPF groups five days before initiation of the treatment procedure. One week after the last injection, mice were sacrificed using anesthetic gas to evaluate alterations in testicular histology and sperm parameters. Seminiferous tubules area and diameter were significantly diminished in the group treated with 5 mg/kg CPF (P<0.05). CPF also statistically reduced sperm parameters (count and motility) and damaged sperm morphology) at both doses (P<0.05). However, NAC significantly improved spermatogonia, spermatocytes, spermatid cell counts as well as sperm parameters in mice treated with both CPF concentrations (P<0.05). According to our results, NAC may significantly ameliorate CPF-induced damages to spermatogonia, spermatocytes, spermatids cell counts and sperm parameters.

Busulfan (BU) has a destructive effect on the male reproductive system. The goal of this study was to assess the effects of olive leaf extract (OLE) as a source of antioxidants and phenolic compounds, on BU-induced damages in rat testes. In this experimental study, 40 male Wistar rats were randomly divided into 5 groups. The control group (CTL) received a single intraperitoneal (i.p.) injection of dimethyl sulfoxide (DMSO), followed by oral administration of distilled water for 5 weeks. In BU group, BU (10 mg/kg) was administrated i.p. once. In co- treatment groups, first, received BU (10 mg/kg, a single i.p. injection) then, OLE was administrated orally at different doses of 250 mg/kg (BU+OLE 250), 500 mg/kg (BU+OLE 500) and 750 mg/kg (BU+OLE 750), for 5 weeks. Next, blood and sperm samples were collected. The left testis was removed to investigate testicular parameters and apop- tosis by using H&E and TUNEL staining, respectively. All data were analyzed by SPSS software and a P<0.05 was considered significant. There was a significant decline in sperm viability (P=0.017), number of primary spermatocyte (PS) (P=0.001) and Leydig cells (P=0.023) in the BU group versus the CTL group. OLE at three doses could repair these defects ver- sus BU group. Increases in apoptotic spermatogonia cells (SG) due to BU were significantly reduced by OLE 250 and 500 mg/kg (P<0.01). A reduction in germinal epithelium height and an increase in apoptotic SG were observed in BU+OLE 750 group vs. other groups (P<0.01) and alkaline phosphatase (ALP) was at the highest level, also Aspartate aminotransferase (AST) increased markedly vs. CTL (P=0.024). Oral administration of OLE at the doses of 250 and 500 mg/kg could be helpful in ameliorating BU- induced toxicity in rat testes, while OLE 750 mg/kg not only did not cause positive effects, but also could exacerbate the harmful effects.

Infertility, one of life’s great stressors, may adversely affect marital satisfaction. No studies have in- vestigated the relationship between perceived stress and marital satisfaction at the dyadic level. The current study assessed the actor and partner effects of perceived stress on marital satisfaction in husband-wife dyads using an in- novative dyadic analysis approach, the Actor-Partner Interdependence Model (APIM). In this cross-sectional study, we recruited a total of 141 infertile couples. Marital satisfac- tion and stress were assessed using the ENRICH Marital Satisfaction Scale (EMS Scale) and Perceived Stress Scale-4 Item (PSS-4), respectively. Dyadic data have been analysed by the APIM approach, with distinguishable dyads. In this approach, actor effect is the impact of a person᾽s perceived stress on his/her own marital satisfaction. Partner effect is the impact of a person's perceived stress on the partner᾽s marital satisfaction. Both men and women’s perceived stress exhibited an actor effect on their marital satisfaction (β=-0.312, P<0.001, β=-0.405, P<0.001, respectively). Women’s perceived stress had a negative relationship to the marital satis- faction of their partner (β=-0.174, P=0.040). Although the partner effect of men’s perceived stress on woman’s marital satisfaction was not significant (β=-0.138, P=0.096), women whose husbands had higher levels of stress were more likely to have poorer marital satisfaction. Both actor and partner effects of perceived stress on marital satisfaction were similar among men and their wives. The findings of this study have highlighted that marital satisfaction in patients with infertility was in- fluenced by not only their own perceived stress, but also their spouses’ perceived stresses. Therefore, psychological interventions that target a reduction in perceived stress and enhancement of marital satisfaction in the context of infer- tility should treat the couple as a unit.

Endometriosis is considered the most common cause of pelvic adhesions in women. Endometriosis- associated adhesions could result in the formation of fibrous bands, which contain endometriotic glands, stroma and scarring. The aim of this study was to identify the impact of endometriosis-related adhesions on quality of life among infertile women. This descriptive study was conducted at Endoscopic Unit, in Zagazig University Hospitals, Egypt. Oral consent for participation in this study was taken from 109 women who were candidates for laparoscopy as infertile cases and were diagnosed with endometriosis. They were classified into two groups namely, group I (n=41) who had endometriosis with adhesions and group II (n=68) who had endometriosis without adhesions. A structured interviewing form, adhesion scoring method of the American Fertility Society, and Global Quality of Life Scale were used to collect required information. The prevalence of adhesions resulted from endometriosis was 37.6%. Demographic characteristics of the women with endometriosis-related adhesions were not significantly different from those of women without endome- triosis-related adhesions. The most common location for endometriotic adhesions was adnexal adhesion (51.2%) fol- lowed by adhesion of anterior abdominal wall (24.4%). Quality of life was significantly impacted by endometriosis- related adhesions (P=0.002). A high percentage of studied patients had a moderate degree of adhesions. Adhesions caused by endo- metriosis had an impact on quality of life of the studied women.

Single nucleotide polymorphisms (SNPs) in a number of genes involved in sperm maturation are considered as one of the main factors for male infertility. The aim of the present case-control study was to examine the association of SNPs in protamine1 (PRM1) and protamine2 (PRM2) genes with idiopathic teratozoospermia. In this case-control study, some SNPs in PRM1 (c.49 C>T, c.102 G>T and c.230A>C) and PRM2 (rs545828790, rs115686767, rs201933708, rs2070923 and rs1646022) were investigated in 30 idiopathic infertile men with teratozoospermia (case group) in comparison with 35 fertile men (controls). Genotyping of SNPs was undertaken using polymerase chain reaction (PCR)-direct sequencing. For PRM1, c.230A>C, as a synonymous polymorphism, was detected in both teratozoo- spermic men (heterozygous n=26, homozygous minor n=1) allele frequency C(48) A(52) and controls (heterozygous n=15, homozygous minor n=4). All cases and controls were genotyped for rs545828790 in PRM2, a missense poly- morphism, as well as rs115686767 and rs201933708, both of which synonymous variants. The findings showed an intronic variant in PRM2 (rs2070923) was also present in both groups. Also, rs1646022, a missense polymorphism, occurred in teratozoospermic men (heterozygous n=10, homozygous minor n=5) and controls (heterozygous n=13, homozygous minor n=2). However, there were no significant differences in SNPs of PRM1 and PRM2 between the two groups, however, for c.230A>C, the frequency of the CA genotype was significantly higher in infertile men with teratozoospermia (P=0.001). We demonstrate that PRM2 G398C and A473C polymorphisms were associated with the teratozoospermia and its genetic variation was in relation to semen quality, sperm apoptosis, and morphology in the Iranian population. This study is a preliminary study and presenting data as part of a future comprehensive study to clinically establish whether these gene polymorphisms are biomarkers for susceptibility to teratozoospermia.

Müllerian anomalies are very common, and a frequent cause of infertility. The most used classification system until now, proposed by the American Society for Reproductive Medicine in 1988, categorizes comprehensively uterine anomalies but fails to classify defects of the cervix or vagina. This is based on a developmental theory that postulates that müllerian duct fusion is unidirectional, beginning caudally and extending cranially, which does not account for isolated cervical or vaginal defects. More recently, the European Society of Human Reproduction and Embryology has developed a consensus, which allows for independent cervical anomalies. We present a case of a 39-year-old woman with secondary infertility, found to have a cervical duplication in an anteroposterior disposition, which puts into question the principles of embryology formerly known, but supports the theory that development happens in a segmentary fashion.