Treatment of Infertility in Women with Polycystic Ovary Syndrome in a Single Center Study

Background: Anovulatory infertility is caused by polycystic ovarian syndrome in 80 percent of patients. Preconception guidelines, such as lifestyle modification (weight loss) to avoid fetal neural tube abnormalities, and quitting smoking and drinking alcohol, are all part of the early treatment. A clomiphene citrate medication for timed intercourse is the first-line pharmacological treatment for producing ovulation. Exogenous gonadotropins or laparoscopic ovarian surgery are two options for second-line pharmaceutical treatment (ovarian drilling). Ovulation induction using clomiphene citrate or gonadotropins is effective, with a 70 % cumulative live birth rate. When laparoscopy is necessary, ovarian drilling should be done; this operation is usually successful in around half of the instances. Finally, when the previous interventions have failed, a high-complexity reproduction treatment (in vitro fertilization or intracytoplasmic sperm injection) is recommended. There is no evidence that metformin should be used routinely in the treatment of infertility in anovulatory women with polycystic ovary syndrome. Aromatase inhibitors show promise, but more research is needed to confirm their safety.Methods:This study was conducted in Department of gynecology and obstetrics, Dhaka Medical College Hospital, Dhaka, from January 2019 to December 2019. A total number of 100 patients with multiple myeloma were analyzed cytogenetically by interphase fluorescence in situ hybridization (iFISH). The collected data were analyzed by using the Statistical Package for Social Science (SPSS-24) for windows version 24.0.Conclusion:PCOS is a frequent syndrome and the most frequent cause of infertility. PCOS is defined as a syndrome with at least two of three of the Rotterdam criteria. A complete evaluation of the infertility is needed to exclude other causes of infertility..

Co-Administration of Clomiphene Citrate and Letrozole in Mild Ovarian Stimulation Versus Conventional Controlled Ovarian Stimulation Among POSEIDON Group 4 Patients

This retrospective study assessed the effect of the co-administration of clomiphene citrate (CC) and letrozole in mild ovarian stimulation, compared to conventional regimens, among Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) Group 4 patients. There were 114 POSEIDON Group 4 patients undergoing in vitro fertilization treatments with 216 stimulation cycles recruited from a Taiwan’s reproductive center during 2016-2020. Main outcomes were the numbers, quality of retrieved oocytes and embryo development. Pregnancy outcomes were assessed after embryo transfers. Per stimulation cycle, patients receiving mild stimulation with a combination of CC and letrozole (study group) versus those with COS (control group) had lower numbers of pre-ovulatory follicles (2.00 ± 1.23 vs. 2.37 ± 1.23, p=0.0066) and oocytes retrieved (1.83 ± 1.17 vs. 2.37 ± 1.23, p=0.0017), and lower follicular output rate (58.6% vs. 68.38%, p=0.0093) and mature oocyte output rate (44.29% vs. 52.88%, p=0.0386) but a higher top-quality metaphase II oocyte ratio (66.7% vs. 54.59%, p=0.0444) and a similar fertilization rate (91.67% vs. 89.04%, p=0.4660). With adjustment for significant between-group baseline differences using multivariable logistic generalized estimating equation model analyses, there was no statistical difference in oocytes retrieved and embryo development between the study and control groups, and insignificant increases in successful pregnancies in the study group were found compared to the control group (i.e., odds ratios [95% CIs]: 1.13 [0.55, 232] and 1.50 [0.65, 3.49] for ongoing pregnancy and live birth, respectively). For POSEIDON Group 4 patients, cotreatment of CC and letrozole in mild stimulation may increase the high-quality oocyte ratio and yield comparable fertilization rate and pregnancy outcomes.

Clomiphene citrate plus letrozole versus clomiphene citrate alone for ovulation induction in infertile women with chronic anovulation: A randomized controlled trial

Objective To compare the efficacy of combination clomiphene citrate (CC) plus letrozole with that of CC alone for ovulation induction in infertile women with chronic anovulation. Material and methods This randomized controlled trial was conducted at the Infertility and Reproductive Biology Unit of the Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand during the August 2020-September 2021 study period. Anovulatory women aged 18-40 years were equally allocated into either the CC 50 mg plus letrozole 2.5 mg once daily group or the CC 50 mg once daily group. The study drugs were administered on days 3-7 of each study patient’s menstrual cycle. The primary outcome was the ovulation rate defined by serum progesterone >3 ng/mL at mid-luteal phase. The secondary outcomes were menstrual cycle characteristics, endometrial thickness, conception rate, and adverse events. Results One hundred women (50 per group) were enrolled. The mean age and prevalence of polycystic ovary syndrome were non-significantly different between groups. The ovulation rate according to intention-to-treat analysis was 78% and 70% in the combination and CC alone groups, respectively (p>0.05). There was no significant difference between groups for either mean endometrial thickness or number of dominant follicles. No serious adverse events were observed in either group. Conclusion There was no significant difference between combination CC plus letrozole and CC alone relative to their ability to induce ovulation in infertile women with chronic anovulation. The small number of live births (1 per group) was too low to be statistically analyzed.

Relationship between pregnancy rate and number of intrauterine insemination cycles during the study of comparative efficacy of letrozole and clomiphene citrate adjuvants to gonadotropin stimulation in controlled ovarian stimulation cycles combined with intrauterine insemination therapy

Background: Infertility is commonly defined as the failure of conception after at least twelve months of unprotected intercourse. Factors contributing are both male and female in which unexplained etiology accounts for 51%, male factor 28%, endometriosis 17% and ovulatory disorders 4%.Methods: Prospective, randomized study was conducted at DRRPG medical college, Tanda, Kangra, Himachal Pradesh. In our study, patients were randomized into two groups of 30 each. Women in group A received clomiphene citrate 100mg/day and group B received letrozole 2.5 mg/day from day 3-7 of menstrual cycle. All the patients received human menopausal gonadotropin 75 U given every alternate day from day 5 until HCG administration. Ovulation was triggered with recombinant HCG (5000 IUIM) when the dominant follicles reached 18 mm in diameter. A single IUI was performed 36 hours later. A maximum of four cycles were given.Results: In our study, total number of induction cycles given in group A and B were 120 and 114 respectively. Out of these, 112 and 111 IUI cycles were done in group A and B respectively. A pregnancy rate of 1.66% and 7.87% per IUI cycle was observed in group A and B respectively.Thus it is concluded that the pregnancy rates were significantly higher in letrozole group (30%) in comparison to clomiphene citrate group (6.66%).Conclusions: Aromatase inhibitor letrozole appears to constitute a good alternative to clomiphene citrate in patients with unexplained infertility undergoing gonadotropin-stimulated COS cycles combined with IUI therapy.

Clomiphene Citrate versus Letrozole for Induction of Ovulation in Infertile women having Polycystic Ovarian Syndrome (Randomized Controlled Trial)

Background: Polycystic ovary syndrome is a disorder but with unclear etiology that its diagnosis depends on exclusion of other etiologies with ovulatory disorders and androgen excess as congenital adrenal hyperplasia, 21-hydroxylase deficient non classic congenital adrenal hyperplasia (NCAH), adrenal or ovarian androgen-secreting tumors, disorders of adrenocortical dysfunction as Cushing’s disease, and abuse of androgenic or anabolic drugs. Polycystic ovary syndrome affects approximately 6-15% of women in reproductive age and constitutes 50% of the causes of infertility in women. Aim of the Work: To compare the efficacy of letrozole on ovulation induction to that of clomiphene citrate in women suffering polycystic ovary syndrome and the effect on the follicular maturation, endometrial thickness and pregnancy rate. This study was carried in the outpatient infertility clinic of Ain-Shams Maternity Hospital during the period from November 2020 till April 2021. Patients and Methods: This study included 80 infertile women diagnosed as having polycystic ovary syndrome. Women were randomized into two groups. Letrozole group (1) included 40 women who were given the aromatase inhibitor (Letrozole) orally in a 5mg dose daily from day 3 to day 7 of the menstrual cycle. While Clomiphene citrate group (2) included 40 women who were given the clomiphene citrate orally in 100mg dose daily from day 3 to day 7 of the menstrual cycle. All women were counseled and informed consent was obtained before recruitment. Results: In this study, ovulation rate was significantly more frequent in the Letrozole group (82.5%, 33 women reached ovulation successfully) than in Clomiphene citrate group (60%, 24 women reached ovulation successfully) within P value=0.024. Clomiphene citrate at a dose of 100mg showed more efficacies in the number of follicle ≥18mm than Letrozole at a dose of 5mg. In Letrozole group, the number of follicles (≥18mm in diameter) ranged from 1 to 2 with a Mean±SD= 1.4±0.65 and in Clomiphene citrate group, the number of follicles (≥18mm in diameter) ranged from 1 to 3 with a Mean±SD= 1.9± 0.41 (P value=0.0001). Conclusion: Letrozole can be considered as a first line treatment of anovulation in polycystic ovary syndrome. But, moreover studies including larger number of cases will further confirm the efficacy of letrozole versus clomiphene citrate in induction of ovulation, reaching to the optimum doses for aromatases inhibitors, more observation on endometrial thickness, incidence of pregnancy outcomes, incidence of abortion and incidence of congenital fetal malformations.

Anti – Androgenic Activity of Caesalpinia bonducella in Androgen-induced Polycystic Ovarian Syndrome Rats

Aim: Our goal was to use the androgen and anabolic steroid (AAS) Testosterone Propionate (TP) to create a novel animal model to study polycystic ovaries. Materials and Methods: Thirty albino female Wistar rats weighing 200 – 250 g were split into five groups with six rats in each group. Group I was treated as standard control, Group II was treated as the PCOS induced group, Group III was treated as a standard group, Clomiphene citrate (20 mg per kg body weight), intraperitoneally (I.P) along with a 4 mg TP injection intramuscularly (I.M) in an oily solution, Group IV was treatment control group treated with a hydro-alcoholic extract of Caesalpinia bonducella (CBHAE) at a dose of 200 mg per kg body weight. Group V was given CBHAE at 400 mg per kg of body weight. Blood collected from animals examined for hormonal parameters and ovaries is subjected to histopathological studies. Results: There was a fall in testosterone volume and an increase in the efflux of female hormone constituents, which improved the ovarian development and helped to regulate menses. Conclusion: Significantly lower levels of Testosterone were produced as a result of the extract, which also showed superior anti-androgenic properties. However, additional intervention is recommended in order to investigate the therapeutic effect of Caesalpinia bonducella seed in further detail.

Clomiphene Citrate and Enclomiphene Hydrochloride Exposure Is Associated With Interfrontal Suture Fusion in Zebrafish

Background: The last several decades have witnessed an increase in metopic craniosynostosis incidence. Population-based studies suggest that pharmacological exposure in utero may be responsible. This study examined effects of the fertility drug clomiphene citrate (CC) on calvarial development in an established model for craniofacial development, the zebrafish Danio rerio. Results: Zebrafish larvae were exposed to clomiphene citrate or its isomer enclomiphene for five days at key points during calvarial development. Larvae were then raised to adulthood in normal rearing water. Zebrafish were analyzed using whole-mount skeletal staining. We observed differential effects on survivability, growth and suture formation depending on the treatment. Treatments with CC or enclomiphene at 5.5 mm SL led to increased fusion of the interfrontal suture (p < .01) compared to controls. Conclusions: Exposure to fertility drugs appears to affect development of the cranial vault, specifically the interfrontal suture, in zebrafish. Further research is required to identify the signaling mechanisms at play. This work suggests that fertility drug treatment may contribute to the increased incidence of metopic craniosynostosis observed globally.