Can Laparoscopic Cystectomy Improve Pregnancy Outcomes in Endometrioma? A Prospective Clinical Trial Study.

BACKGROUND: The purpose of this prospective study was to compare the ovarian response and pregnancy outcomes
in the infertile women with endometrioma undergoing assisted reproductive technologies (ART) in two
groups, who were underwent laparoscopic cystectomy and received gonadotropin releasing hormone-agonist
(GnRH-agonist) and who only received GnRH-agonist without any surgery.
Materials and Methods: In this prospective clinical trial study, 79 infertile women with asymptomatic endometriomas
cyst (2-6 cm) were enrolled and randomly assigned to two groups. First group underwent laparoscopic
cystectomy and received GnRH-agonist. Second group only received GnRH-agonist without any surgery. Following
ovulation induction, all patients underwent intracytoplasmic sperm injection (ICSI). Different parameters
such as the number of retrieved oocytes and embryos; were made our outcomes that analyzed using SPSS.
Results: The pregnancy rate, chemical and clinical, and live birth rate were higher in the combined group,
although these differences were not statistically significant (48.48% vs. 30.8%, P=0.12, 36.36% vs. 25.6%,
P=0.32, 36.36% vs. 23.1%, P=0.29). The number of injections, antral follicles, retrieved oocytes, mature oocytes,
total embryos, transferred embryos and duration of stimulation were similar in two groups.
Conclusion: Laparoscopic cystectomy followed by receiving GnRH-agonist improves pregnancy outcomes in endometrioma
prior to treatment with ART (registration number: IRCT201106116689N2).

Metformin improves epigenetic modification involved in oocyte growth and embryo development in polycystic ovary syndrome mice model.

The possible relationship between dehydroepiandrosterone (DHEA)-induced polycystic ovary syndrome (PCOS) and epigenetic changes (ECs) leading to the impaired oocyte quality, has not been investigated yet. So, this study aimed to provide an insight into the relationship of the impaired oocyte quality with ECs in a mice DHEA-induced PCOS model and to further reveal the effect of metformin treatment. For this purpose, 80 female BALB/C mice were randomly divided into four equal groups, named as the control, sham, (DHEA) and DHEA + Metformin groups. The alterations in acetylation of H4K5 and H4K16, and in methylation of DNA (5MeC) and H3K9 were evaluated using immunocytochemical. Moreover, the expression of Hdac1, Hdac2, Dnmt1, and Dnmt3a genes involved in ECs were analyzed using reverse-transcription polymerase chain reaction. As well, the levels of mitochondrial membrane potential (MMP), oxidative stress (OS), embryo development, ovarian morphology, sexual hormone, ovulatory function, and AMPKα phosphorylation activity were compared in all the studied groups. Metformin attenuated the damages induced by DHEA as indicated by the normalized the estrous cycle, the improved ovarian morphology, the decreased sexual hormone and OS levels, and the increased MMP and AMPKα phosphorylation levels. In the metformin group, the Dnmt1, Dnmt3a, and Hdac2 genes have significantly upregulated compared to the DHEA group. However, metformin was found to have no effect on the expression level of Hdac1. In this regard, significant decrease and increase were observed in both the acetylated H4K16 and methylated H3K9 within MII oocytes in the DHEA + Metformin group compared with the DHEA group. Our results show that metformin could enhance the developmental competence of PCOS oocytes via reducing OS and ECs.

The effects of letrozole and clomiphene citrate on ligands expression of Wnt3, Wnt7a, and Wnt8b in proliferative endometrium of women with Polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is a common endocrinologic disorder in women of reproductive age characterized by polycystic ovaries, oligo/anovulation, and hyperandrogenism. Not only anovulation but also endometrial dysfunction can reduce fertility in PCOS patients. Wnt pathway is responsible for endometrial proliferation which be strongly regulated by estradiol. To determine the effects of clomiphene citrate (CC) and letrozole, we measured the expression of some main ligands of Wnt/ß-catenin signaling including Wnt7a, Wnt3, and Wnt8b in the endometrial samples taken from PCOS women on day 12 of the menses who received 100 mg CC or 5 mg letrozole as well as from women without treatment. Significantly, the mean estrogen and progesterone concentration were lower and higher, respectively, in letrozole than CC. The mean endometrial thickness (ET) was significantly greater in letrozole compared to CC. Assessment of the mRNA and protein expression of Wnt7a, Wnt3, and Wnt8b showed significantly lower expression in CC than the letrozole and control groups. Collectively, letrozole provided a better molecular response in the endometrium of PCOS patients during the proliferative phase, similar to natural cycles, compared to CC. CC decreased the ligands expression of Wnt3, Wnt7a, and Wnt8b, resulting in endometrial dysfunction.

Expression of AKT1 along with AKT2 in granulosa-lutein cells of hyperandrogenic PCOS patients.

PURPOSE: AKTs have a pivotal role in the granulosa-lutein cell (GC) proliferation and folliculogenesis, and there is a reciprocal feedback between AKT with androgen. Therefore, we aimed to evaluate the role of AKTs in GCs of hyperandrogenic (+HA) PCOS cases. METHOD: There were three groups: control, +HA PCOS and -HA (non-hyperandrogenic) PCOS. All groups were subjected to GnRH antagonist protocol for stimulation of ovulation. Follicular fluid was aspirated from large follicles, and GCs were isolated using cell strainer method. AKT1, AKT2, AKT3, and androgen receptor (AR) mRNA expressions were analyzed with quantitative real-time PCR (qRT-PCR), and total-AKT and p-AKT (Ser473 & Thr308) were investigated using western blotting. RESULTS: There were high levels of AKT1, AKT2, and AR mRNA expressions and high levels of p-AKT protein expression in the +HA PCOS group (p ≤ 0.05). There was a direct positive correlation between free testosterone (FT) and total testosterone (TT) with the levels of AKT1, AKT2, and p-AKT (Ser473), and also between FT with the levels of AR. CONCLUSION: High expressions of AKT1 and AKT2 through possible relation with androgen may cause GCs dysfunction in the +HA PCOS patients.

Hysteroscopy in patients with repeated implantation failure improves the outcome of assisted reproductive technology in fresh and frozen cycles.

AIM: Repeated implantation failure (RIF) is still a problem for many patients and their physicians. Some interventions have been practiced to overcome the problem; one is uterine cavity assessment before assisted reproductive technology (ART) cycles. This study aimed to evaluate the effect of hysteroscopy in women experiencing recurrent implantation failure with apparently normal uterine cavity before assisted reproductive techniques. MATERIAL AND METHODS: This was a cohort study with historical controls conducted in a university hospital. A total of 353 women with RIF undergoing ART with normal hysterosalpingography and transvaginal ultrasound were evaluated. The intervention group underwent hysteroscopy with a rigid, 30°, 4-mm hysteroscope in the menstrual cycle just before ART; in the control group hysteroscopy was not performed. Basal characteristics, stimulation parameters and pregnancy rates were compared between the two groups. RESULTS: Chemical pregnancy occurred in 58.5% of women in the hysteroscopy group versus 34.1% of control women (odds ratio [OR]: 2.7; 95% confidence interval [CI]: 1.7-4.2; P < 0.001). Clinical pregnancy occurred in 50.7% and 30.3% of women in the hysteroscopy and control groups, respectively (OR: 2.4; 95%CI: 1.5-3.7; P < 0.001). Delivery rate was 35.5% in hysteroscopy women and 21.1% in control women (OR: 1.9; 95%CI: 1.2-3.1; P = 0.008). The results of hysteroscopy were normal in 103 women (72.5%), and they revealed inflammation in 22 (15.5%), polyp in 16 (11.3%) and Asherman syndrome in one patient (0.7%). CONCLUSIONS: Hysteroscopy in the menstrual cycle before ovarian stimulation in fresh cycles and before endometrial preparation in frozen thawed cycles in women experiencing recurrent implantation failure with apparently normal uterine cavity significantly increases the pregnancy rates in fresh and frozen cycles, respectively.

Treatment of ovarian hyperstimulation syndrome using gonadotropin releasing hormone antagonist: a pilot study.

OBJECTIVE: This novel study describes an effective outpatient treatment for ovarian hyperstimulation syndrome (OHSS) that results in rapid normalization of symptoms. STUDY DESIGN: A total of twenty-seven infertile women undergoing assisted reproductive technique with early-onset OHSS were enrolled in this non-randomized clinical trial in an academic infertility center. In all patients, after complete desensitization with long-term protocol ovarian stimulation with gonadotropins was commenced. Final oocyte maturation was triggered with human chorionic gonadotrophin. Oocytes were collected 36-38 h later using transvaginal-guided follicle aspiration under general anaesthesia. All embryos were frozen and study group patients received two consecutive doses of GnRH antagonist (Cetrotide) and the control group received daily dose of cabergoline for a week. RESULTS: The research revealed that moderate and severe OHSS, hospitalization or acute care for OHSS and ascites tap were significantly lower in the antagonist (Cetrotide) group. The Patients' satisfaction with Cetrotide was noticeable. No side effect was reported in either group. CONCLUSION: GnRH antagonists seem to be an effective outpatient treatment with rapid onset activity and minimal side effects for the management of early OHSS.

Local injury to the endometrium does not improve the implantation rate in good responder patients undergoing in-vitro fertilization.

BACKGROUND: Despite numerous developments in the field of assisted reproduction the implantation rate remains low .Recent studies suggested that local injury to endometrium in controlled ovarian hyper stimulation cycle improves implantation rate. Studies have attempted to intervene in the development of endometrium. OBJECTIVE: The aim of the present study was the exploration of the possibility that local injury of the endometrium increases implantation rate. MATERIALS AND METHODS: In this interventional study, 100 good responders to hormone stimulation patients were divided into control group (n=50) and experimental group (n=50) which undergo endometrial biopsy by biopsy catheter )piplle) on day 21 of their previous menstrual cycle with use of contraceptive pills before the IVF-ET treatment. In total, 26 patients were removed from the study because the number of stimulated follicles were below 3, or there was no embryo or there was the risk of OHSS. The remaining patients were 33 in experimental group and 41 in the control group. RESULTS: There were no significant differences between the two groups in terms of the age of the patients, duration of infertility and BMI, base line FSH level and responses to hormone stimulation. The rates of embryo implantation, chemical and clinical pregnancy in the experimental group were 4.9%, 18.2% and 12.1% with no significant differences with the control group (6.7%, 19.5%, 17.1%). Cancellation rate was 26%. CONCLUSION: In our study, endometrial biopsy didn't increase the chances to conceive at the following cycle of treatment.

Secondary amenorrhea with low serum luteinizing hormone and follicle-stimulating hormone caused by an inhibin A- and inhibin B-producing granulosa cell tumor.

OBJECTIVE: Here, we report a case of secondary amenorrhea with low serum luteinizing hormone and follicle-stimulating hormone levels due to an inhibin A- and inhibin B-producing granulosa cell tumor of the ovary. CASE REPORT: A woman aged 26 with infertility, secondary amenorrhea and low levels of gonadotropin was referred to us as a case of hypothalamic amenorrhea. There was a mass measuring 56 x 41 mm in her right adnexa. We were suspicious of malignancy and checked the tumor marker levels. Laboratory findings showed high levels of inhibin A and B. She underwent an exploratory laparotomy. Microscopic examination revealed an adult granulosa cell tumor. Eighteen days after excision, she had spontaneous menstruation with normal levels of follicle-stimulating hormone and luteinizing hormone. CONCLUSION: A granulosa cell tumor secretes inhibin A and B, which suppress follicle-stimulating hormone and luteinizing hormone release through a central mechanism. This leads to amenorrhea, which can be misdiagnosed as hypothalamic amenorrhea. Inhibin producing ovarian tumors must be considered in the assessment of patients with apparent hypothalamic amenorrhea.

The effects of L-carnitine on sperm parameters in smoker and non-smoker patients with idiopathic sperm abnormalities.

PURPOSE: To determine the effects of L: -carnitine on sperm parameters in patients with idiopathic sperm abnormalities. METHODS: In an academic reproductive care center, 170 patients including 48 smokers and 122 non-smokers participated in a before-after study. Men were given 1 g of L: -carnitine orally 3 x daily for 3 months. Sperm assessment was done before and after the treatment. Main outcome measures were sperm concentration, motility, and morphology before and after the treatment. RESULTS: L-Carnitine was effective in improvement of percentile of motile sperms, grade A sperms, and normal-shaped sperms. L-Carnitine significantly improved percentile of motile and grade A sperms in non-smokers. Only the change in the median percentile of normal forms was within the significant range in smokers. CONCLUSIONS: The results of this study indicate that smoker patients should not be excluded from the treatment with L-carnitine based on smoking alone.