A randomized controlled trial comparing pioglitazone and metformin prior to in vitro fertilization in polycystic ovary syndrome - associated infertile women: impact on pregnancy rates.

Background: Polycystic ovarian syndrome (PCOS) is one of the significant causes of infertility. Impaired glucose metabolism and insulin resistance add chiefly to the pathogenesis of PCOS. This study aimed to evaluate the efficacy of metformin and pioglitazone (insulin sensitizers) on the quality of the ovum and pregnancy rate in the IVF cycle. Methods: In this randomized clinical trial study, 172 infertile women with PCO were enrolled and randomly assigned to receive either 15 mg pioglitazone (case group) or 1000 mg metformin (control group) twice a day for 6 weeks before IVF, and the pregnancy rate was compared across the groups. The number of ovum and embryos were also accessed and compared between the two groups. Results: In the study, 172 patients participated. The mean age in the control and case groups was 32.09±3.9 years and 32.12±3.9 years, respectively, with no significant age difference. In both groups, the mean number of IVF eggs retrieved was 11.76±3.7 (control) and 11.86±3.7 (case), and the number of embryos formed was 7.43±2.8 (control) and 7.87±3.5 (case), with no significant disparities (P<0.05). Regarding positive pregnancies, 28 out of 86 (32.6%) occurred in the control group, while 42 out of 86 (48.8%) happened in the case group, demonstrating a significant difference (P=0.03). Conclusions: According to the results obtained in this study, it may be concluded that pioglitazone is superior to metformin in IVF cycles in PCOS-associated infertile women leading to a higher pregnancy rate.

Effects of clomiphene citrate plus estradiol or progesterone on endometrial ultrastructure: An RCT.

BACKGROUND: Pinopods concentrations in endometrial surface is a marker of implantation. Estradiol valerate (EV) was used to change the adverse effects of Clomiphene Citrate (CC) on the endometrium. OBJECTIVE: The goal was to assess whether there is a significant difference in the endometrial pinopods concentrations and other parameters after adding EV and progesterone to higher doses of CC. MATERIALS AND METHODS: In this prospective randomized clinical trial, a total of 30 women who did not respond to 100 mg of CC from February 2016 to June 2016 were evaluated. They were divided into three groups: group I) received 150 mg of CC alone, group II) CC with EV, and group III) CC plus progesterone. On day 21 of the menstrual cycle, endometrial biopsy, a blood sampling, and a scanning by electron microscopy were performed. RESULTS: On day 21 of the menstrual cycle, there was no significant difference in the pinopods concentrations (p = 0.641) and serum estrogen levels (p = 0.276) between groups. However, the Serum progesterone levels in group I was higher than the other two groups (p = 0.007) in the same day. CONCLUSION: Since the addition of EV and progesterone to higher dosages of CC did not change the pinopods concentration and serum estrogen levels on day 21 of the menstrual cycle, and the serum progesterone levels was higher in CC alone group (i.e. group I) compared to other groups, it can be concluded that the anti-estrogenic effects of CC just appear on the endometrium and not on the plasma levels.

Are intra follicular estradiol and oocytes quality in women undergoing assisted reproductive technology different between the right and left ovaries? An observational study.

OBJECTIVE: Controlled Ovarian Stimulation (COS) for In-Vitro Fertilization (IVF) or Intracytoplasmic Sperm Injection (ICSI) is considered as an assisted reproduction technology. There are established structural and biological differences between both ovaries which may affect their responsiveness to COS. Whether the right or the left ovary responds superior to COS is a question which is unresolved in the literature. STUDY DESIGN: The present study was conducted as a prospective observational to make a comparison between right and left ovaries' oocytes based on oocyte quality and follicular fluid estradiol level. A total of 100 infertile women who had referred to Infertility and Reproductive Health Research center at Shahid Beheshti University of Medical Sciences, Tehran, Iran, were investigated. RESULTS: The total number of very good and good oocytes were 63.01% vs. 50.3%, and immature and interstitial oocytes were 36.99% vs. 49.6% in the right and the left ovaries, respectively. There were no significant differences between oocyte rates between the two ovaries (P > 0.05). CONCLUSION: Good and very good quality oocytes and fertilization rate (P < 0.001) are higher in the right ovary compared with the left ovary; however, no significant difference was observed between the right and the left ovaries in oocyte yields and cleavage rates. Moreover, despite higher follicular estradiol levels in the left ovary, there was no relationship noticed between follicular fluid estradiol and oocyte quality among oocytes of each ovary.

Comparison of First Trimester Screening for Down's Syndrome Using Free Beta-Human Chorionic Gonadotropin and Pregnancy-Associated Plasma Protein-A Levels between Spontaneous and IVF Pregnancies at 12 Weeks of Gestation.

BACKGROUND: In some previous studies, it was shown that first trimester screening tests produce equivocal results in in vitro fertilization (IVF) pregnancies. The purpose of this study was to compare free beta-human chorionic gonadotropin (ß-hCG) and pregnancy-associated plasma protein-A (PAPPA) levels between single normal and IVF pregnancies during 11 to 13 week (+ 6 day) of gestational age. MATERIALS AND METHODS: In this observational cohort study, 300 consecutive single IVF pregnancies and 700 single normal pregnancies were enrolled at about 11-13 week + 6 day gestational age and levels of free ß-hCG and PAPPA were compared between the groups. RESULTS: The results demonstrated that PAPPA (P=0.026) was significantly lower and ß-hCG (P=0.030) was significantly higher in IVF pregnancies. The other factors including nuchal translucency (NT) and crown-rump length (CRL) and demographic characteristics did not significantly differ between the groups (P>0.05). CONCLUSION: This study showed that PAPPA levels are lower but free ß-hCG levels are higher in single IVF versus normal pregnancies. This finding could be related to different placentation in intracytoplasmic sperm injection (ICSI) technique because of alterations in oocyte cytoplasm. Therefore, these markers may need to be adjusted in assisted reproductive technology (ART) conceptions. Further research should be done to obtain optimal cut-off for these markers in first trimester screening for detection of Down syndrome in ART pregnancies.

Comparison of Cabergoline and Quinagolide in Prevention of Severe Ovarian Hyperstimulation Syndrome among Patients Undergoing Intracytoplasmic Sperm Injection.

BACKGROUND: The aim of the current study is to compare quinagolide with cabergoline in prevention of ovarian hyperstimulation syndrome (OHSS) among high risk women undergoing intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: This randomized clinical trial study was performed from March 2015 to February 2017. One hundred and twenty six women undergoing ICSI who were at high risk of developing OHSS (having over 20 follicles of >12 mm), were randomized into two groups. The first group received cabergoline 0.5 mg and the second group received quinagolide 75 mg every day for 7 days commencing on the day of gonadotropin-releasing hormone (GnRH) agonist administration. Then OHSS symptoms as well as their severity were assessed according to standard definition, 3 and 6 days after GnRH agonist administration. Ascites were determined by trans-vaginal ultrasound. Other secondary points were the number of oocytes and the number of embryos and their quality. Quantitative and qualitative data were analyzed using Student's t test, and Chi-square or fisher's exact test, respectively. A P<0.05 was considered statistically significant. RESULTS: The incidence of severe OHSS in the quinagolide-treated group was 3.1% while it was 15.8% in cabergolinetreated subjects (P<0.001). Ascites were less frequent after treatment with Quinagolide as compared to cabergoline (21.9% vs. 61.9%, respectively) (P=0.0001). There was no significant statistical deferences between the two groups in terms of mean age, number of oocytes, metaphase I and metaphase II oocytes, and germinal vesicles. There was a significant difference between cabergoline and quinagolide groups regarding the embryo number (P=0.037) with cabergoline-treated group showing a higher number of embryos. But, the number of good quality embryo in quinagolide- treated individuals was significantly higher than that of the cabergoline-treated group (P=0.001). CONCLUSION: Quinagolide seems to be more effective than Cabergoline in prevention of OHSS in high-risk patients undergoing ICSI. (Registration number: IRCT2016053128187N1).

Comparing the effect of gonadotropin-releasing hormone agonist and human chorionic gonadotropin on final oocytes for ovulation triggering among infertile women undergoing intrauterine insemination: An RCT.

BACKGROUND: The purpose of triggering in ovulation induction is to induce the final maturation of oocytes and their release from the ovary for fertilization. OBJECTIVE: The aim of the present study was to compare the effectiveness of gonadotropin-releasing hormone (GnRH) agonist and human chorionic gonadotropin (HCG) on the final maturation of oocytes and pregnancy rates in intrauterine insemination (IUI) cycles. MATERIALS AND METHODS: In this randomized clinical trial, 110 infertile women who were selected for IUI entered the study. Ovulation induction was performed. Group I received 0.1 mg GnRH agonist as triggering and group II received 10,000 IU of HCG. The serum E2, LH, and FSH levels were measured at 12 and 36 hr after injection. RESULTS: LH surge was detected in all patients. LH levels at 12 and 36 hr after triggering was higher in Group I and it washed out earlier than group II (p=0.00). The pregnancy rate was higher in Group I, but the difference was not statistically significant (26.9% vs. 20.8%, respectively p=0.46). Also, the incidence of ovarian hyperstimulation syndrome was not different between the two groups (p=0.11). There was a significant difference regarding the estradiol levels at 36 hours after triggering (p=0.00). CONCLUSION: Effects of GnRH on endogenous LH surge is sufficient for oocyte releasing and final follicular maturation. Pregnancy rates and ovarian hyperstimulation syndrome incidence were not different between the groups. We suggest that GnRH agonists might be used as an alternative option instead of HCG in IUI cycles.

Comparison of oral dydrogesterone with vaginal progesteronefor luteal support in IUI cycles: a randomized clinical trial.

BACKGROUND: The aim of this study, we have compared the advantages of oral dydrogestrone with vaginal progesterone (cyclogest) for luteal support in intrauterine insemination (IUI) cycles. Progesterone supplementation is the first line treatment when luteal phase deficiency (LPD) can reasonably be assumed. OBJECTIVE: This study was conduct to compare the effect of oral dydrogestrone with vaginal Cyclogest on luteal phase support in the IUI cycles. MATERIALS AND METHODS: This prospective, randomized, double blind study was performed in a local infertility center from May 2013 to May 2014. It consisted of 150 infertile women younger than35years old undergoing ovarian stimulation for IUI cycles. They underwent ovarian stimulation with oral dydrogesterone (20 mg) as group A and vaginal cyclogest (400 mg) as group B in preparation for the IUI cycles. Clinical pregnancy and abortion rates, mid luteal progesterone (7daysafter IUI) and patient satisfaction were compared between two groups. RESULTS: The mean serum progesterone levels was significantly higher in group A in comparison with group B (p=0.001). Pregnancy rates in group A was not statistically different in comparison with group B (p =0.58). Abortion rate in two groups was not statistically different (p =0.056) although rate of abortion was higher in group B in comparison with A group. Satisfaction rates were significantly higher in group A compared to group B (p<0.001). CONCLUSION: We concluded that oral dydrogestrone is effective as vaginal progesterone for luteal-phase support in woman undergoing IUI cycles. Moreover, the mean serum progesterone levels and satisfaction rates in dydrogestrone group were higher than cyclogest group.