International Journal Of Fertility and Sterility
Volume:9 Issue: 2, Jul-Sep 2015

Varicocele is characterized by abnormal tortuosity and dilation of the veins of the pampiniform plexus within the spermatic cord. Although several reports show the mechanisms by which the varicocele exerts its infertility impact, the exact pathophysiology for varicocele-induced inflammation and its relationship with testicular endocrine disruption remain largely unknown. This review article will update previous findings by discussing the pathophysiology of long term-induced varicocele in rats. Testicular endocrine disruption in experimentally-induced varicocele, new findings related to biochemical alterations in germinal epithelium, and sperm cells apoptosis are highlighted. Recent observations show that varicocele down-regulates first and second maturation divisions, results in Leydig and Sertoli cell inflammation, and increases immune cell infiltration in the testes of the rat as an animal model. Ultimately, previous findings of our laboratory have revealed that varicocele decreased sperm motility, viability and severe DNA damage. Damage in sperm significantly lowers the animal’s fertility potential. Varicocele not only exerts its pathologic impact by lowering the testicular antioxidant capacity but it also down-regulates first and second maturation divisions by exerting biochemical alterations such as reducing the intracytoplasmic carbohydrate ratio in germinal epithelium.

The relationship between metabolism and reproduction has been always considered as an important topic in female endocrinology. It seems that leptin is one of the involved factors in infertility. Leptin, in addition to regulating body weight plays an important role in regulation of endocrine, reproductive and immune systems. The aim of this stduy is to compare serum and follicular fluid leptin concentrations in order to find the role of leptin level in infertility. This case-control study was performed from September 2010 to March 2013. A total of 90 women referred to the Infertility Center of Afzalipour Hospital, Kerman, Iran, and divided into three equal groups (n=30/per group) of explained infertile (including 4 subgroups), unexplained infertile and normal fertile (control group). The three groups were matched in regard to demographic features [age: 20-40 years and body mass index (BMI): 20-25]. In order to determine leptin level, blood sample and follicular fluid were taken one hour prior and at the time of follicular puncture, respectively. Serum and follicular fluid leptin levels were measured using enzyme-linked immune sorbent assay (ELISA). Data were analyzed using descriptive-analytic tests, like Mann- Whitney and Kruskal Wallis tests, through Statistical Package for the Social Sciences (SPSS) version 16. In explained infertile and fertile groups, as opposed to unexplained infertile group, mean leptin level was lower in follicular fluid than in serum. Mean follicular fluid leptin concentration in women with unexplained infertility was higher compared to the other two groups. Women with unexplained infertility had lower level of serum leptin in comparison to the other two groups. Follicular fluid leptin level in all subgroups of explained infertile group was lower as compared to unexplained and fertile women. The results suggested that high leptin level of follicular fluid is one of the main factors involved in infertility.

Evaluation of anti-mullerian hormone (AMH) cut-off levels in assisted reproductive technology (ART) as predictive factor for individualization of stimulation protocols and to avoid ovarian hyperstimulation syndrome (OHSS). In a retrospective study, 177 infertile patients were assessed for AMH in serum and follicular fluid (FF) on the day of follicular puncture (FP), between 2012 and 2013 in Kiel, Germany. AMH levels and pregnancy rates were compared between low, moderate and high responders and cut-off levels of low and high responders. AMH cut-off levels in pathological cases were evaluated in analysis 1 (OHSS) and in analysis 2 [polycystic ovarian syndrome, (PCOS)] and compared in analysis 3 to normal endocrinological parameters. AMH levels in FF were higher than in serum (P<0.001). AMH levels in serum and FF increased from low through moderate to high responders (P<0.001). Pregnancy rates were 14.7, 23.3 and 44.9% (P=0.009), respectively. AMH cut-off level for poor responders was 0.61 ng/ml in serum with a pregnancy rate of 13.8 and 37.1% for below and above of this level, respectively. For FF, it was 1.43 ng/ml. AMH levels in analysis 1 and 2 were significantly higher than in analysis 3 (P=0.001). AMH cut-off level for OHSS was 1.5 ng/ml in serum with OHSS rates of 80.8 and 19.2 % for above and below of the level, respectively. For FF, it was 2.7 ng/ml. PCOS patients had an AMH cut-off level of 3.9 ng/ml in serum and 6.8 ng/ml in FF, resulting in a PCOS rate of 100% above this level. AMH levels can help to assess ovarian response potential and guide ovarian stimulation while avoiding OHSS.

Hysteroscopy offers diagnostic accuracy and the ability to treat uterine pathology. The current study aimed to review the findings and feasibility of the proposed office-based diagnostic and operative microhysteroscopy in previously diagnosed women with unexplained infertility and to evaluate the post-microhysteroscopic pregnancy outcome in a-year follow-up period. This prospective controlled study was conducted between 2006 and 2013. Two hundreds women with unexplained infertility were randomized into two groups: A. study group including 100 women recruited for office micohysteroscopic session and B. control group including 100 without the proposed microhysteroscopic intervention. A malleable fiberoptic 2-mm, 0 and 30 degrees angled hysteroscopy along with an operative channel for grasping forceps, scissors, or coaxial bipolar electrode were used for both diagnostic and operative indications. The findings, complications, and patient tolerance were recorded. A-year follow-up of pregnancy outcome for both groups was also performed. Seventy cases (70%) of patients had a normal uterine cavity. Twenty women (20%) had endometrial polyps. Other pathology included submucous myomas in 3 cases (3%), intrauterine adhesions in 3 cases (3%), polypoid endometrium in 3 cases (3%), and bicornuate uterus in one case (1%). The pathological findings were treated in all patients without complication. Also a-year follow-up of the total developing cumulative pregnancy rate (CPR) was evaluated in groups A and B (control). Group A revealed the total CPR of 28.5%, among which 25% in women without pathology, 40% in women with endometrial polyps, 23% in women with adhesions, 33% in women with polypoid endometrium, and 21% in those with bicornuate uterus. However, A-year follow-up of spontaneous pregnancy outcome in group B showed a total CPR of 15%. Women tolerance, safety, and feasibility of simultaneous operative correction make the proposed office microhysteroscopy an ideal and routine procedure in order to diagnose and to treat missed intrauterine abnormalities, especially in cases with unexplained infertility, with additional improvement of the pregnancy outcome after the procedure.

We aimed to estimate the glomerular filtration rate (GFR) in women with polycystic ovary syndrome (PCOS) and to determine the relationship between GFR with C-reactive protein (CRP) and uric acid. In this cross-sectional study, one-hundred and forty PCOS women and 60 healthy subjects were evaluated. The study was carried out at Endocrinology Outpatient Clinic, Erzurum Training and Research Hospital, Erzurum, Turkey, from December 2010 to January 2011. GFRs were estimated by Modification of Diet in Renal Disease (MDRD) formula. CRP, urinary albumin excretion (UAE) and uric acid levels were also measured. GFRs were significantly higher in PCOS group than control (135.24 ± 25.62 vs. 114.92 ± 24.07 ml/min per 1.73 m2). CRP levels were significantly higher in PCOS patients (4.4 ± 3.4 vs. 2.12 ± 1.5 mg/l). The PCOS group had significantly higher serum uric acid levels (4.36 ± 1.3 mg/dl vs. 3.2 ± 0.73 mg/dl). There was also significantly higher proteinuria level in PCOS patients. Even though PCOS patients had higher GFR, serum uric acid and UAE values than control patients, the renal function was within normal limits. Increased GFR in PCOS women positively correlates with elevated serum CRP and uric acid.

Endometriosis is a complex disease with a spectrum of pain symptoms from mild dysmenorrhea to debilitating pelvic pain. There is no concrete evidence in the literature whether endometriotic cyst per se, causes pain spectrum related to the disease. The aim of the present study was to evaluate the effect of surgical removal of endometriomas on pain symptoms. In this prospective, observational, before-after study, which was conducted between March 2012 and January 2013 in Training and Research Hospital,Adana, Turkey, a total of 23 patients including 16 sexually active and 7 virgin symptomatic women were questioned for non-cyclic pelvic pain (NCPP), intensity of the NCPP, presence of cyclic dysmenorrhea, and dyspareunia before and after the endometrioma operation. Participants who were sonographically diagnosed and later pathologically confirmed as having endometrioma without sign and symptoms of deep infiltrative endometriosis (DIE) were also questioned for pain symptoms before and after the laparoscopic removal of cyst wall. Patients with intraabdominal adhesions, history of pelvic inflammatory disease, and pathological diagnosis other than endometrioma were excluded. No ancillary procedures were applied for pain management, but if pain was present, pelvic peritoneal endometriotic lesions were ablated beside the removal of ovarian endometriotic cysts. Out of 23 cases with endometrioma, 91 and 78% reported to have NCPP and dysmenorrhea, respectively, before the operation, while 60 and 48%, respectively, after the operation (McNemar’s test, P=0.016 for both figures). Among the sexually active cases, 31% (5/16) had dyspareunia before the operation and only 1 case reported the pain relief after the operation (McNemar’s test, P=1). Intensity of NCPP were reported to be none (8.7%), moderate (21.7%), severe (56.5%) and unbearable (13%) before the operation and decreased to none (43.5%), mild (43.5%), moderate (4.3%) and severe (8.7%) after the operation (Wilcoxon signed-rank test, P<0.001). In symptomatic cases with ovarian endometrioma, without sign and symptoms of DIE, laparoscopic removal of the cysts with/without ablation of the peritoneal endometriotic lesions yields relief of NCPP and cyclic dysmenorrhea, but not dyspareunia.

The androgen receptor (AR) gene contains a polymorphic trinucleotide repeat that encodes a polyglutamine tract in its N-terminal transactivation domain (NTAD). We aimed to find a correlation between the length of this polymorphic tract and azoospermia or oligozoospermia in infertile men living in Khuzestan, Iran. In this case-control study during two years till 2010, we searched for microdeletions in the Y chromosome in 84 infertile male patients with normal karyotype who lived in Khuzestan Province, Southwest of Iran. All cases (n=12) of azoospermia or oligozoospermia resulting from Y chromosome microdeletions were excluded from our study. The number of CAG repeats in exon 1 of the AR gene was determined in 72 patients with azoospermia or oligozoospermia and in 72 fertile controls, using the polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis. Microdeletions were detected in 14.3% (n=12) patients suffering severe oligozoospermia. The mean CAG repeat length was 18.99 ± 0.35 (range, 11-26) and 19.96 ± 0.54 (range, 12-25) in infertile males and controls, respectively. Also in the infertile group, the most common allele was 19 (26.38%), while in controls, it was 25 (22.22%). Y chromosome microdeletions could be one of the main reasons of male infertility living in Khuzestan Province, while there was no correlation between CAG length in AR gene with azoospermia or oligozoospermia in infertile men living in Khuzestan, Iran.

The omega-3 fatty acid (ω-3 fatty acid) such as eicosapentaenoic acid (EPA) is currently used in the clinic as a nutritional supplement in the treatment of polycystic ovarian syndrome (PCOS). The present study was designed to investigate the effect of EPA on the expression levels of peroxisome proliferator-activated receptor gamma (PPARγ) and cytochrome P450 aromatase (encoded by the CYP-19) in primary cultured granulosa cells (GC) from patients undergoing in vitro fertilization (IVF), and also to compare these effects with those in GC of PCOS patients. In this experimental study, human GC were isolated, primary cultured in vitro, exposed to a range of concentrations of the EPA and investigated with respect to gene expression levels of PPARγ and CYP-19 using real time-polymerase chain reaction (PCR). The participants (n=30) were the patients admitted to the IVF Center in February-March 2013 at Alzahra Hospital, Tabriz, Iran, who were divided into two groups as PCOS (n=15) and non-PCOS (n=15) women (controls). All doses of the EPA significantly induced PPARγ mRNA gene expression level as compared to the control recombinant follicle stimulating hormone (rFSH) alone condition. High doses of EPA in the presence of rFSH produced a stimulatory effect on expression level of PPARγ (2.15-fold, P=0.001) and a suppressive effect (0.56-fold, P=0.01) on the expression level of CYP-19, only in the PCOS GC. EPA and FSH signaling pathway affect differentially on the gene expression levels of PPARγ and CYP-19 in PCOS GC. Altered FSH-induced PPARγ activity in PCOS GC may modulate the CYP-19 gene expression in response to EPA, and possibly modulates the subsequent steroidogenesis of these cells.

During spermatogenesis, the H2B family, member W (H2B.W) gene, encodes a testis specific histone that is co-localized with telomeric sequences and has the potential role to mediate the sperm-specific chromatin remodeling. Previously H2B.W genetic variants were reported to be involved in susceptibility to spermatogenesis impairment. In the present study, two single nucleotide polymorphisms (SNPs) in 5΄UTR and exon 1 of H2B.W gene were examined to investigate possible association of these polymorphisms with male infertility in Iranian population. This case control study was conducted in Royan institute during four-year period (2010–2013). Genetic alteration of two SNPs loci, −9C>T and 368A>G, in H2B.W gene were indicated in 92 infertile men who were divided into two main groups including azoospermia (n=46) and sever oligozoospermia (n=46), while there was 60 fertile men as control group. Azoosperima was also divided into three sub-groups including sertoli cell only syndrome (SCOS, n=21), complete maturation arrest (CMA, n=17) and hypo spermatogenesis (n=8) according to testicular biopsy. For analysis, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was applied. The frequency of allele −9T was significantly higher in CMA group than in patients with SCOS (P<0.05). The haplotype TA (corresponding to simultaneous occurrence of −9T and 368A) compared with haplotype CA (corresponding to simultaneous occurrence of −9C and 368A) in patients suffering from CMA significantly increased, compared with patients had SCOS (P<0.05). However, statistical studies indicated that in general, the distribution frequencies of −9C>T and 368A>G had no significant difference between the infertile groups and control (P=0.859 and P=0.812, respectively). This investigation showed that SNP −9C>T might be contribute to CMA in azoospermic patients and SNP 368A>G had no correlation with male infertility in Iranian population.

Embryo morphology has been proposed as an alternative marker of chromosomal status. The objective of this retrospective cohort study was to investigate the association between the chromosomal status on day 3 of embryo development and blastocyst morphology. A total of 596 embryos obtained from 106 cycles of intracytoplasmic sperm injection (ICSI) followed by preimplantation genetic aneuploidy screening (PGS) were included in this retrospective study. We evaluated the relationship between blastocyst morphological features and embryonic chromosomal alteration. Of the 564 embryos with fluorescent in situ hybridization (FISH) results, 200 reached the blastocyst stage on day 5 of development. There was a significantly higher proportion of euploid embryos in those that achieved the blastocyst stage (59.0%) compared to embryos that did not develop to blastocysts (41.2%) on day 5 (P<0.001). Regarding blastocyst morphology, we observed that all embryos that had an abnormal inner cell mass (ICM) were aneuploid. Embryos with morphologically normal ICM had a significantly higher euploidy rate (62.1%, P<0.001). As regards to the trophectoderm (TE) morphology, an increased rate of euploidy was observed in embryos that had normal TE (65.8%) compared to embryos with abnormal TE (37.5%, P<0.001). Finally, we observed a two-fold increase in the euploidy rate in high-quality blastocysts with both high-quality ICM and TE (70.4%) compared to that found in low-quality blastocysts (31.0%, P<0.001). Chromosomal abnormalities do not impair embryo development as aneuploidy is frequently observed in embryos that reach the blastocyst stage. A high-quality blastocyst does not represent euploidy of chromosomes 13, 14, 15, 16, 18, 21, 22, X and Y. However, aneuploidy is associated with abnormalities in the ICM morphology. Further studies are necessary to confirm whether or not the transfer of blastocysts with low-quality ICM should be avoided.

Timing of the first zygotic cleavage is an accurate predictor of embryo quality. Embryos that cleaved early (EC) have been shown to exhibit higher developmental viability compared to those that cleaved at a later period (LC). However, the viability of EC embryos in comparison to LC embryos after vitrification is unknown. The present study aims to investigate the post-vitrification developmental viability of murine EC versus LC embryos. In this experimental study, female ICR mice (6-8 weeks old) were superovulated and cohabited with fertile males for 24 hours. Afterwards, their oviducts were excised and embryos harvested. Embryos at the 2-cell stage were categorized as EC embryos, while zygotes with two pronuclei were categorized as LC embryos. Embryos were cultured in M16 medium supplemented with 3% bovine serum albumin (BSA) in a humidified 5% CO2 atmosphere. Control embryos were cultured until the blastocyst stage without vitrification. Experimental embryos at the 2-cell stage were vitrified for one hour using 40% v/v ethylene glycol, 18% w/v Ficoll-70 and 0.5 M sucrose as the cryoprotectant. We recorded the numbers of surviving embryos from the control and experimental groups and their development until the blastocyst stage. Results were analyzed using the chi-square test. A significantly higher proportion of EC embryos (96.7%) from the control group developed to the blastocyst stage compared with LC embryos (57.5%, P<0.0001). Similarly, in the experimental group, a significantly higher percentage of vitrified EC embryos (69.4%) reached the blastocyst stage compared to vitrified LC embryos (27.1%, P<0.0001). Vitrified EC embryos are more vitrification tolerant than LC embryos. Preselection of EC embryos may be used as a tool for selection of embryos that exhibit higher developmental competence after vitrification.

Cryopreservation of semen requires optimized conditions to minimize the harmful effects of various stresses. The main approach for protection of sperm against stress is based on the use of antioxidants and cryoprotectants, which are described as defensive methods. Recently, the application of controlled mild stressors has been described for activation of a temporary response in oocyte, embryo and somatic cells. In this study a sub-lethal oxidative stress induced by precise concentrations of nitric oxide (NO) has been evaluated for sperm during cryopreservation. In this experimental study, we used different concentrations of NO [0 μM (NO-0), 0.01 μM (NO-0.01), 0.1 μM (NO-0.1), 1 μM (NO-1), 10 μM (NO-10) and 100 μM (NO-100)] during cryopreservation of bull semen. Their effects on post-thawed sperm quality that included motility and velocity parameters, plasma membrane functionality, acrosome integrity, apoptosis status, mitochondrial activity and lipid peroxidation after freezing-thawing were investigated. Exposure of sperm before freezing to NO-1 significantly increased total motility (88.4 ± 2.8%), progressive motility (50.4 ± 3.2%) and average path velocity (VAP, 53.8 ± 3.1 μm/s) compared to other extenders. In addition, NO-1 significantly increased plasma membrane functionality (89.3 ± 2.9%) compared to NO-0 (75.3 ± 2.9%), NO-0.01 (78.3 ± 2.9%), NO-0.1 (76.4 ± 2.9%), NO-10 (64 ± 2.9%) and NO-100 (42 ± 2.9%). Sperm exposed to NO-1 produced the highest percentage of viable (85.6 ± 2.3%) and the lowest percentage of apoptotic (10.8 ± 2.4%) spermatozoa compared to the other extenders. Also, NO-100 resulted in a higher percentage of dead spermatozoa (27.1 ± 2.7%) compared to the other extenders. In terms of mitochondrial activity, there was no significant difference among NO-0 (53.4 ± 3.2), NO-0.01 (52.1 ± 3.2), NO-0.1 (50.8 ± 3.2) and NO-1 (53.1 ± 3.2). For acrosome integrity, no significant different was observed in sperm exposed to different concentrations of NO. Induction of sub-lethal oxidative stress with 1 μM NO would be beneficial for cryopreservation of bull semen.

The purpose of this study is to investigate the efficacy of emotionally focused therapy (EFT-C) on promoting marital adjustment of infertile couples with marital conflicts by improving quality of life. This is a semi-experimental study with a pre- and post–test design in which 30 infertile couples (60 individuals) were chosen by purposive sampling. Couples were randomly divided into two groups, sample and control, of 15 couples each. Next, couples in the sample population answered questionnaires for marital adjustment, sexual satisfaction and quality of life after which they received 10 sessions of EFT-C. Pre- and post-tests showed that EFT-C had a significant effect on marital adjustment and quality of life. According to the results, EFT-C had a significant, positive effect on enhancement of marital adjustment. Life quality of infertile couples significantly increased via application of EFT-C. This approach improved the physical, psychological and social relationships of infertile couples and enhanced their social environment.

Postpartum depression (PPD) is one public health issue that affects both maternal and child health. This research studies the effect of health volunteers’ telephonebased support on decreasing PPD. This randomized controlled trial evaluated 203 women who had uncomplicated deliveries. The women completed the Edinburg Postnatal Depression Scale (EPDS), 10 to 15 days after childbirth in order to be assessed for pre-trial depression scores. The cut-off point for depression was considered to be a score of >10. We randomly assigned 54 eligible mothers (n=27 per group) with mild and moderate depression to the intervention and control groups. In both groups, mothers received routine postpartum care. The intervention group additionally received telephone support from health volunteers. A questionnaire was used to gather demographic and obstetric information. By the end of the 6th week, mothers completed the EPDS to be reassessed for depression after intervention. Data were analyzed using the chi-square, Fisher’s exact, t- and paired t tests. The mean depression scores before intervention (10 to 15 days after childbirth) in the intervention and control groups did not significantly differ (P=0.682). Depression scores of the intervention and control groups showed a significant difference after 6 weeks (P=0.035). In addition, there was a significant decrease in depression for the intervention and control groups (P=0.045). Health volunteer telephone-based support effectively decreased PPD and may be beneficial to women with symptoms of mild and moderate PPD (Registration number: IRCT201202159027N1).

Embryo donation was one of the infertility treatment methods introduced to the Iranian legal system in 2003 (Act of Embryo Donation) and its by-law passed in 2005 after numerous discussions. Embryo donation is a new legal issue in Iran. No similar act has been previously legislated in the legal system; however, on the other hand, the importance of the judicial procedure in its execution cannot be ignored since during this treatment process the infertile couples must refer to the court. In this paper, we analyzed 80 court decisions that concerned permission for embryo donation during 2006-2011. The decisions were made for couples who requested this treatment and referred to Avicenna Fertility Center (Tehran, Iran). In this study, we analyzed the decisions and regulations for the demands, in addition to the medical and legal viewpoints of the judges. The differences among the judges’ decisions and in the ways of investigating were discussed.

Endometrial adenocarcinoma (EC) usually occurs after menopause, whereas in 2-14% of cases, it occurs in young patients (less than 40 years old) who may desire to keep their fertility. It is of importance to evaluate women for EC when they develop polycystic ovarian syndrome and abnormal uterine bleeding. Its treatment includes hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy and in some cases, radiation therapy. We report a case of EC in a 31-year-old woman who presented to Royan Institute. She complained about oligomenorrhea with a 10-year history of primary infertility.

A 35 year-old woman at 7-week gestational age was referred to our hospital. The patient was diagnosed with the heterotopic interstitial pregnancy by transvaginal ultrasonography after receiving in vitro fertilization (IVF) and embryo transfer. Laparoscopic excision and curettage was successfully performed at 8.4-gestational age under general anesthesia and the patient was discharged 2 days after operation without any post-operative complications. The woman had normal antenatal follow-up and delivered a healthy baby at term by cesarean section.