Therapeutic Effect of Vitamin D3 Supplementation to Clomiphene Citrate Resistant PCOS Women: A Randomized Controlled Trial

Background Polycystic ovary syndrome (PCOS) is considered one of the most common endocrine disorders affecting females in their reproductive age. In PCOS, an imbalance between androgens, anti-Müllerian hormone (AMH) and follicle stimulating hormone (FSH), cause a halt of follicular growth. Insulin resistance (IR) is another important component of PCOS. There is increasing evidence that vitamin D affects insulin and glucose metabolism, Vitamin D plays a vital role in the regulation of glucose-insulin homeostasis. Objectives to assess the efficacy of vitamin D supplementation in improving ovulation induction in PCOS women (1ry outcome) and increasing pregnancy rate (secondary outcome). Patients and Methods 120 women diagnosed PCOS according to Rotterdam criteria and were resistant to CC treatment were randomly allocated into equal two groups: Group V: number of 60 patients received cholecalciferol + Metformin for 2 months. Group C: 60 patients received Metformin 2 months. After two months from the start:Both study groups started induction with Clomiphene Citrate added every month starting from the 3rd month to the 5th month (3 cycles of ovulation induction) in addition to previous drugs mentioned. Results In our study results, regulation of menstrual cycle occured in 63.6% of women who recieved vitamin D + metformin (group V) and ovulation was confirmed in 34.5% of the total number (55 women). Later, 18% of them got pregnant after 3 months of treatment. Added to that 16 women out of 39 (41%) got pregnant by the end of the follow up period with cumulative pregnancy rate (53%). On the other hand menstrual regularity in (group C: metformin) recorded 61% with ovulation percentage of 26.9% (n = 54). Followed by 14.8% pregnancy rate at the 3rd month., which increased to 27.5% by the end of the study out of 47.5% ovulated women (n = 40). Cumulative pregnancy rate 40%. Conclusion From the current study we can conclude that there is no significant difference of adding vitamin D to CC resistant PCOS regarding ovulation and pregnancy rates. However, it can augment metformin action and improves its outcome.

P–122 Benefit of use of theophilline in ICSI with testicular sperm

Study question Would the use of theophylline have an effect on ICSI outcomes? Summary answer The cumulative pregnancy rate after the transfer of fresh and frozen embryos (FET) becomes more important justifying the addition of theophylline as an efficacy variable. What is known already Absolute immotile spermatozoa is one of the most important causes of reduced fertilization and pregnancy rates after ICSI, immotility of testicular spermatozoa is a physiological event resulting from metabolic sperm immaturity. Over the years, there have been numerous attempts to resolve this problem by identification of pharmacological agents that might improve sperm motility. In particular, theophylline turned out to be an effective tool in stimulating motility in human semen and identifying viable sperm in testicular sperm extraction sperm (TESE) patients. aim of this study is to evaluate ICSI outcomes after the use of theophylline to select viable spermatozoa Study design, size, duration This prospective, comparative randomised study was conducted in Fertillia ART center in Tunisia, between november 2017 to november 2020. All patients underwent ICSI cycles with testicular sperm were included. The exclusion criteria consist of cycles with female partner age >42 years and/or cycles with no information about pregnancy outcomes. In our study, the cycles were categorized into two groups according to sperm selection method used in ICSI procdure. Participants/materials, setting, methods The present study include 678 cycles. This cohort was randomly divided into two groups according to method of spermatozoa selection. Treatements arms were performed by theophylline to improve sperm motility (Group A) and the Hyposmotic swelling (HOS) test to indicate sperm vitality (Group B). Clinical and biological parameters, the duration of sperm selection and ICSI outcomes were compared between the two groups. A statistical significant difference was accepted when the p value was <0.05. Main results and the role of chance Baseline clinical parameters were found to be comparable in the two groups. No differences regarding number of oocytes retrieved or MII oocytes were reported . he sperm selection was easier in the group A (time interval : 12±7,2 minutes) than group B (time interval : 22±10 minutes) (p < 0,05). No significative difference was observed between goups in the Fertilization rate (group A : 66% vs group B : 68%) ; Cleavage rate (group A : 76.20% vs. Group B : 75.56%) and Blasulation rate (group A : 63.60% vs. Group B 60.61%) p > 0 ,05. The Cumulative Pregnancy rate for group A (31. 5%) was higher than group B (30%, p > 0 ,05). Indeed, The rate of frozen cycles is significantly higher for group A compared to group B (30% vs. 4.5% p < 0,05). Limitations, reasons for caution Need large sample size. Wider implications of the findings: Theophylline reduces significantly the time needed for sperm selection, Which positively affects the ICSI result. Trial registration number Not applicable

P–611 Innovative controlled ovarian stimulation (COS) for polycystic ovary syndrome (PCOS) produces high-quality oocytes and no ovarian hyper stimulation syndrome (OHSS)

Study question How can we find an ovarian stimulation method that does not cause hyper stimulation syndrome but can produce a high pregnancy rate at one cycle? Summary answer This newly developed method for PCOS has a higher accumulative clinical outcome for one trial and no OHSS. What is known already Almost all conventional treatments for PCOS have managed to avoid OHSS by reducing the number of growing follicles, which are associated with high Estradiol levels and stimulate the production of vessel endothelial growth hormone (VEGF), leading to increased vessel permeability. Low dose FSH administration, In vitro maturation (IVM), Ovarian Drilling and Coasting have been performed to achieve this. However, their actual clinical outcome is still unsatisfactory. Study design, size, duration Evaluation of the efficiency of this method was conducted retrospectively at St. Mother Clinic. The embryonic development and the clinical outcome were studied for 34 PCOS patients during the period between November 2018 and December 2019. Participants/materials, setting, methods We started injections of FSH (150iu/ml), then we did ultrasound follicle monitoring. GnRH antagonist shots were started when the leading follicle reached 18mm and continued until the largest follicle was 22–24mm and the E2 value was over 4000pg/ml. Letrozole (2.5mg) and leuprorelin acetate (1.88mg) was injected as trigger. Two tablets each of Letrozole, Cabergoline and GnRH antagonist were given for 5 consecutive days after the oocyte retrieval. All embryos were cryopreserved. Main results and the role of chance Number of patients and cycles were 34 and 59. Average number of cryopreserved blastocysts was 6.12 (1–16). The frequencies of OHSS (mild, moderate, severe) were 29.4% (10/34), 0% (0/34), 0% (0/34). Average days between oocyte collection and withdrawal hemorrhage was 5.44(5–7). Cryopreservation rate was 100.0% (34/34). Clinical pregnancy rate and miscarriage rate was 42.3% (25/59) and 16.0% (4/25). The cumulative pregnancy rate was 73.7% (25/34). The four remaining unsuccessful cases still have 10,6,3 and 7 frozen embryos. So, there is a high possibility that they become successful, that would bring the cumulative pregnancy rate up to 82.3% (28/34). Limitations, reasons for caution This COS for PCOS seems promising, however it is premature to conclude that this method is established. This method requires caution monitoring for hormone level, follicle size and number and coagulant function. It also accompanied with the risk of ovarian hemorrhage on aspiration of a great number of oocytes. Wider implications of the findings: This COS seems viable for PCOS cases. It could control the cohort of antral follicles with different doses of Letrozole to find the optimal COH method and it could become the first option for COS of PCOS. Trial registration number N/A

Predictive Factors of Conception and the Cumulative Pregnancy Rate in Subfertile Couples Undergoing Timed Intercourse With Ultrasound

The aim of this study was to determine predictive factors for pregnancy and assess the cumulative pregnancy rate (CPR) and live birth rate (CLBR) in subfertile couples undergoing timed intercourse (TI) using ultrasound. This retrospective cohort study included 285 women (854 cycles) who started TI with ultrasound between January 2017 and October 2019. The overall clinical pregnancy rate was 28.1% (80/285) per couple and 9.4% (80/854) per cycle. Pregnant women had a higher body mass index (BMI), higher percentage of irregular menstrual cycles, a shorter duration of subfertility, lower serum follicle-stimulating hormone levels, and higher anti-Müllerian hormone levels than non-pregnant women. A longer duration of subfertility (≥24 months vs. <12 months; odds ratio: 0.193; 95% confidence interval: 0.043-0.859) and endometriosis (vs. ovulatory factors; odds ratio: 0.282; 95% confidence interval: 0.106-0.746) as causes of subfertility were unfavorable factors that independently affected clinical pregnancy. In subgroup analysis, old age ≥ 35 years [vs. < 35 years; odds ratio: 0.279; 95% confidence interval: 0.083-0.938), a longer duration of infertility ≥24 months (vs. <24 months; odds ratio: 0.182; 95% confidence interval: 0.036-0.913) and a higher BMI ≥ 25 kg/m2(vs. >25 kg/m2; odds ratio: 3.202; 95% confidence interval: 1.020-10.046) in couples with ovulatory factor and a longer duration of infertility ≥24 months (vs. <24 months; odds ratio: 0.185; 95% confidence interval: 0.042-0.819) in couples with non-ovulatory factors were significant independent predictive factors for pregnancy. No significant differences were found in the cycle characteristics between pregnant and non-pregnant women. The CPR substantially increased during the first three cycles and significantly increased until the sixth cycle. No significant increase was observed in the CPR after the sixth cycle. The CLBRs substantially increased during the first three cycles and significantly increased until the fourth cycle. No significant increase was observed in the CLBRs after the fifth cycle. When comparing CPRs and CLBRs according to subfertile causes, CRPs was significantly different and CLBRs was different with borderline significance. Our findings may indicate that women with a longer duration of subfertility or subfertility due to endometriosis have poor outcomes during TI with ultrasound. Women who failed to achieve conception by the fourth or fifth cycle of TI with ultrasound may be encouraged to consider advancing to the next treatment strategy.

Pretreatment maternal lifestyle and outcomes of assisted reproduction: an Italian cohort study

ObjectiveWe investigated whether lifestyle affects assisted reproduction technology (ART) outcomes.DesignCohort study.SettingItalian fertility unit.ParticipantsFrom September 2014 to December 2016, women from couples presenting for evaluation and eligible for ART were invited to participate. Information on alcohol intake, current smoking and leisure physical activity (PA) during the year before the interview was collected, using a structured questionnaire. We considered the ART outcomes of the cycle immediately following the interview.Primary and secondary outcome measuresThe primary outcome measure was cumulative pregnancy rate per retrieval. Secondary measures were number of retrieved oocytes, embryo transfer and live birth.ResultsIn 492 women undergoing an ART cycle, 427 (86.8%) underwent embryo transfer, 157 (31.9%) had at least one clinical pregnancy and 121 (24.6%) had live birth. The cumulative pregnancy rate per retrieval was 33.3% (95% CI 28.5% to 38.7%). In women in the third tertile of alcohol intake, adjusted relative risk was 0.97 (95% CI 0.87 to 1.08), 0.90 (95% CI 0.62 to 1.30) and 0.89 (95% CI 0.57 to 1.37) for embryo transfer, clinical pregnancy and live birth, respectively. The corresponding figures in women currently smoking more than 5 cigarettes/day were 1.00 (95% CI 0.88 to 1.16), 0.94 (95% CI 0.60 to 1.48) and 1.14 (95% CI 0.68 to 1.90), and in women with PA ≥5 hours/week were 0.93 (95% CI 0.79 to 1.08), 0.44 (95% CI 0.22 to 0.90) and 0.48 (95% CI 0.22 to 1.05), respectively.ConclusionThere were no significant differences in in vitro fertilisation outcomes among women who used alcohol or tobacco in the year prior to treatment. Conservatively, all women should be advised to limit substance abuse. Moreover, our study suggested that maintaining a moderate, but not high, level of PA could be beneficial.

Spontaneous pregnancy rate after saline infusion sonogram treat done under high pressure

Background: Failure to achieve conception after 12 months of regular unprotected intercourse is defined as infertility. The aim of this study was evaluating SIS done under high pressure (SIStreat) as a treatment procedure, for relieving simple tubal obstruction and on cumulative pregnancy rate in infertile women.Methods: A prospective, interventional trial was done (October 2017 - November 2018) on 106 eligible women. All patients performed SIS. Patient with tubes patent under low pressure were assigned as control group, the rest of them were subjected to SIStreat, this group was farther divided into Group 2-a (patent under high pressure) and Group 2-b (occluded under high pressure). All patients had regular intercourse for 6 months. Pregnancy was confirmed by serum B-HCG.Results: we compared patients who performed conventional SIS (n = 100 cases) to patients who performed SIStreat afterwards (n = 84) according to the number of patent tubes. There was a high statistically significant difference in favor of SIStreat group (p < 0.001). Also, there was no significant difference in pregnancy rate between control group 62.5% and Group 2-a 45.7% (p = 0.226).Conclusions: SIStreat is a whole new procedure for opening fallopian tubes (diagnosed occluded by SIS). Patients who were successfully treated by SIStreat had cumulative pregnancy rate comparable to patients who were diagnosed to have patent tubes using conventional SIS.

Effect of Utilization of Single or Double Prostaglandin Administration Within an Ovsynch Fixed-Time Artificial Insemination Protocol During Summer Season in Dairy Cows

This study investigated the fertility of dairy cows during summer season after treatment with a single or double PGF2α in a progesterone (P4)-based Ovsynch protocol for fixed-time artificial insemination (FTAI). The data were compared to a treatment effectuated during winter season. Two groups of 60 dairy cows each were randomly assigned on day 60 post-partum to single PGF2α or double PGF2α group. At removal of the P4 treatment the single PGF2α group received a single dose and the double PGF2α group received two doses of PGF2α at 24 hours apart. In each group, 30 cows were treated during the summer (June, July and August) and 30 cows during the winter (December, January and February) season. During summer season a double PGF2α dose did not influence pregnancy rate at FTAI but improved cumulative pregnancy rate 60 days after FTAI (43% vs 69% for single PGF2α and double PGF2α administration, respectively; P<0.05). During winter season the single or double PGF2α administration did not modify PR or cumulative PR. In conclusion, during summer the utilization of a double instead of single PGF2α treatment into a P4-based Ovsynch-FTAI protocol did not increase pregnancy rate at FTAI but improved cumulative pregnancy rate.

Pre-pregnancy maternal fasting plasma glucose levels in relation to time to pregnancy among the couples attempting first pregnancy

STUDY QUESTION What is the relationship between pre-pregnancy maternal glucose levels and fecundability in Chinese couples? SUMMARY ANSWER Elevated pre-pregnancy maternal glucose levels were associated with fecundability, as reflected by prolonged time to pregnancy (TTP) among the couples with no prior gravidity. STUDY DESIGN, SIZE, DURATION Based on the National Free Pre-conception Check-up Projects supported by the Chinese government, 2 226 048 eligible couples attempting first pregnancy and participating in the project from 2015 to 2016 were included. They were followed-up for 1 year or until they reported pregnancy. PARTICIPANTS/MATERIALS, SETTINGS, METHODS The Kaplan–Meier method was used to estimate the cumulative pregnancy rate in each menstrual cycle, and the discrete-time analogue of the Cox models was used to estimate the fecundability odds ratios (FORs) and 95% CIs by different pre-pregnancy maternal glucose levels (impaired fasting glucose (IFG) or diabetes as compared to normal). MAIN RESULTS AND THE ROLE OF CHANCE The cumulative pregnancy rate for 12 cycles of the normal fasting plasma glucose (FPG) level group was 42.29%, significantly higher than that of the IFG (35.52%) and diabetes groups (31.52%). After adjusting for confounding factors, the FORs were 0.82 (95% CI: 0.81–0.83) and 0.74 (95% CI: 0.72–0.76) for the IFG and diabetes groups, respectively, as compared to the normal group. The association between pre-pregnancy maternal FPG levels and the FORs was non-linear, and the optimal FPG level for greatest fecundability (shortest TTP) was 3.90–4.89 mmol/L. LIMITATIONS, REASONS FOR CAUTION The findings from this register-based cohort study require cautious interpretation given that information bias would be inevitable for single FPG measurements and for TTP calculations that were based on telephone follow-up information. Additionally, because couples who achieved pregnancy during their first menstrual cycle in the study were excluded, the pregnancy rates reported were low and possibly biased. WIDER IMPLICATIONS OF THE FINDINGS The current report suggests that elevated pre-pregnancy maternal glucose levels were associated with prolonged TTP. Early evaluation and preventive treatment for female partners with IFG or diabetes in a pre-pregnancy examination are necessary. STUDY FUNDING/COMPETING INTEREST(S) Funding was provided by the National Key Research and Development Program of China (grants No. 2016YFC1000300 and 2016YFC1000307), the National Natural Science Foundation of China (grant No. 81872634), the CAMS Innovation Fund for Medical Sciences (grant No. 2018-I2M-1-004), the National Human Genetic Resources Sharing Service Platform (grant No. 2005DKA21300) and the National Population and Reproductive Health Science Data Center (grant No. 2005DKA32408), People’s Republic of China. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A