Basal Anti Mullerian hormone levels and endometrial thickness at midcycle can predict the outcome after clomiphene citrate stimulation in anovulatory women with PCOS, a retrospective study

Abstract Purpose Recent studies reported that in polycystic ovary syndrome (PCOS) patients, other stimulation agents are superior to the popular first-line regimen, clomiphene citrate (CC) for ovarian stimulation. Nonetheless, CC is still widely used since it is not clear which patients will not respond to it. Furthermore, the prognostic value of endometrium thickness at midcycle is controversial. We aimed to find factors predicting the response to CC and the prognostic value of endometrial thickness at midcycle. Methods We collected data retrospectively from 89 anovulatory PCOS patients who had the first stimulation with 50 mg CC. We analyzed the basal levels of AMH, testosterone, LH, LH:FSH ratio and the endometrial thickness at midcycle by univariate, followed by multivariate regression. The outcome measures were pregnancy, follicle maturation and endometrial thickness at midcycle. Results Stimulation with 50 mg CC resulted in follicle maturation in 50.6% of the women and in 27.0% pregnancies. In the univariate analysis, greater endometrial thickness, lower LH and AMH levels and a lower LH:FSH ratio were associated with pregnancy (p < 0.05). In the multivariate analysis, only endometrial thickness remained predictive (p = 0.045). The endometrial thickness cutoff level of ≥ 8 mm showed a sensitivity of 87.5% (96% CI 67.6–97.3) and a specificity of 66.7% (95% CI 43.0–85.4) for prediction of pregnancy. In the multivariate analysis AMH levels 5.4 (3.4; 7.0) (ng/mL) predicted pregnancy (β = − 0.194 ± 0.092; p = 0.034) Conclusion We suggest to refrain from CC as first-line regimen in patients with AMH > 7 ng/ml. Under CC treatment, the cutoff value of ≥ 8 mm endometrium thickness at midcycle is associated with a better outcome.

Download Full-text

Comparative study of clomiphene citrate versus letrozole as first-line ovulation induction drug in infertile polycystic ovary syndrome women

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20202738 ◽

2020 ◽

Vol 9 (7) ◽

pp. 2948

Author(s):

Mahija Sahu ◽

Nihar Ranjan Rout

Keyword(s):

Polycystic Ovary Syndrome ◽

Pregnancy Rate ◽

Ovulation Induction ◽

Polycystic Ovary ◽

Endometrial Thickness ◽

Clomiphene Citrate ◽

Ovulation Rate ◽

First Line ◽

Ovary Syndrome ◽

Standard Drug

Background: Polycystic ovary syndrome is the commonest endocrinopathy resulting in anovulatory infertile young women. Clomifene citrate (clomiphene) is a long-standing standard drug for ovulation induction, and is still considered as first line option in PCOS women. However, clomiphene has certain disadvantage letrozole an aromatase inhibitor acts by reducing estrogen production and has no adverse effects on endometrium and cervical mucous. Indian PCOS women have high prevalence of insulin resistance and thus are likely to have high clomiphene resistance. So letrozole could prove to be a good alternative for ovulation induction in such women.Methods: This was a prospective randomized, parallel, comparative clinical trial of two ovulation induction drugs letrozole 5 mg versus clomiphene citrate 100 mg as first-line ovulation induction drug in infertile polycystic ovarian syndrome women. The target population of the study was one hundred infertile women with PCO (taking at least 2 Rotterdam’s parameters). 50 women were allocated to clomifene citrate and 50 were allocated to Letrozole for ovulation induction. Parameters like age, duration of infertility, B MI, ovulation rate, number of follicles, pregnancy rate, endometrial thickness were noted and analyzed.Results: In letrozole group, the ovulation rate, mono-follicular development, mean endometrial thickness and pregnancy rate was better in comparison to clomifene citrate group.Conclusions: The result of this study suggests that letrozole may replace clomiphene as the first line drug for ovulation induction in infertile PCOS women.

Download Full-text

Prospective Parallel Randomized, Double-Blind, Double-Dummy Controlled Clinical Trial Comparing Clomiphene Citrate and Metformin as the First-Line Treatment for Ovulation Induction in Nonobese Anovulatory Women with Polycystic Ovary Syndrome

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2005-0110 ◽

2005 ◽

Vol 90 (7) ◽

pp. 4068-4074 ◽

Cited By ~ 176

Author(s):

Stefano Palomba ◽

Francesco Orio ◽

Angela Falbo ◽

Francesco Manguso ◽

Tiziana Russo ◽

...

Keyword(s):

Polycystic Ovary ◽

Clomiphene Citrate ◽

Controlled Clinical Trial ◽

Line Treatment ◽

First Line ◽

Ovary Syndrome ◽

Double Blind ◽

Group A ◽

Group B ◽

First Line Treatment

Abstract Context: Although metformin has been shown to be effective in the treatment of anovulation in women with polycystic ovary syndrome (PCOS), clomiphene citrate (CC) is still considered to be the first-line drug to induce ovulation in these patients. Objective: The goal of this study was to compare the effectiveness of metformin and CC administration as a first-line treatment in anovulatory women with PCOS. Design: We describe a prospective parallel randomized, double-blind, double-dummy controlled clinical trial. Setting: The study was conducted at the University “Magna Graecia” of Catanzaro, Catanzaro, Italy. Patients: One hundred nonobese primary infertile anovulatory women with PCOS participated. Interventions: We administered metformin cloridrate (850 mg twice daily) plus placebo (group A) or placebo plus CC (150 mg for 5 d from the third day of a progesterone withdrawal bleeding) (group B) for 6 months each. Mean outcome measures: The main outcome measures were ovulation, pregnancy, abortion, and live-birth rates. Results: The subjects of groups A (n = 45) and B (n = 47) were studied for a total of 205 and 221 cycles, respectively. The ovulation rate was not statistically different between either treatment group (62.9 vs. 67.0%, P = 0.38), whereas the pregnancy rate was significantly higher in group A than group B (15.1 vs. 7.2%, P = 0.009). The difference found between groups A and B regarding the abortion rate was significant (9.7 vs. 37.5%, P = 0.045), whereas a positive trend was observed for the live-birth rate (83.9 vs. 56.3%, P = 0.07). The cumulative pregnancy rate was significantly higher in group A than group B (68.9 vs. 34.0%, P < 0.001). Conclusions: Six-month metformin administration is significantly more effective than six-cycle CC treatment in improving fertility in anovulatory nonobese PCOS women.

Download Full-text

A Review of First Line Infertility Treatments and Supporting Evidence in Women with Polycystic Ovary Syndrome

Medical Sciences ◽

10.3390/medsci7090095 ◽

2019 ◽

Vol 7 (9) ◽

pp. 95 ◽

Cited By ~ 2

Author(s):

Michael Costello ◽

Rhonda Garad ◽

Roger Hart ◽

Hayden Homer ◽

Louise Johnson ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Ovulation Induction ◽

Polycystic Ovary ◽

Clomiphene Citrate ◽

Multiple Pregnancy ◽

Reproductive Age ◽

Supporting Evidence ◽

First Line ◽

Ovary Syndrome ◽

Ultrasound Monitoring

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of reproductive age. Lifestyle change is considered the first line treatment for the management of infertile anovulatory women with PCOS, and weight loss for those who are overweight or obese. First line medical ovulation induction therapy to improve fertility outcomes is letrozole, whilst other less efficacious ovulation induction agents, such as clomiphene citrate, metformin, and metformin combined with clomiphene citrate, may also be considered. Metformin combined with clomiphene citrate is more effective than clomiphene citrate alone. In obese women with PCOS, clomiphene citrate could be used in preference to metformin alone whilst clomiphene citrate could be added to metformin alone in order to improve reproductive outcome in all women with PCOS. Gonadotrophins, which are more effective than clomiphene citrate in therapy naïve women with PCOS, can be considered a first line therapy in the presence of ultrasound monitoring, following counselling on the cost and the potential risk of multiple pregnancy.

Download Full-text

Minimal stimulation or clomiphene citrate as first-line therapy in women with polycystic ovary syndrome: a randomized controlled trial

Gynecological Endocrinology ◽

10.3109/09513590.2011.589924 ◽

2011 ◽

Vol 28 (2) ◽

pp. 87-90 ◽

Cited By ~ 6

Author(s):

Hatem Abu Hashim ◽

Mohamed Bazeed ◽

Ibrahim Abd Elaal

Keyword(s):

Randomized Controlled Trial ◽

Polycystic Ovary ◽

Controlled Trial ◽

Clomiphene Citrate ◽

First Line ◽

Ovary Syndrome ◽

Randomized Controlled ◽

First Line Therapy ◽

Line Therapy ◽

Minimal Stimulation

Download Full-text

Ovulation induction in women with polycystic ovary syndrome: randomized trial of clomiphene citrate versus low-dose recombinant FSH as first line therapy

Reproductive BioMedicine Online ◽

10.1016/s1472-6483(10)61273-4 ◽

2004 ◽

Vol 9 (4) ◽

pp. 382-390 ◽

Cited By ~ 40

Author(s):

Eugenio López ◽

Gunby Joanne ◽

Salim Daya ◽

Juan J Parrilla ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Ovulation Induction ◽

Low Dose ◽

Polycystic Ovary ◽

Clomiphene Citrate ◽

Recombinant Fsh ◽

First Line ◽

Ovary Syndrome ◽

First Line Therapy ◽

Line Therapy

Download Full-text

Impact of Luteal phase clomiphene citrate on endometrial thickness and clinical pregnancy rates in women with polycystic ovary syndrome

Obstetrics & Gynecology International Journal ◽

10.15406/ogij.2020.11.00503 ◽

2020 ◽

Vol 11 (3) ◽

pp. 158-161

Author(s):

Elsayed Elshamy ◽

Ayman Soliman

Keyword(s):

Polycystic Ovary Syndrome ◽

Luteal Phase ◽

Polycystic Ovary ◽

Endometrial Thickness ◽

Clomiphene Citrate ◽

Clinical Pregnancy ◽

Ovary Syndrome ◽

Clinical Pregnancy Rates ◽

Group 2 ◽

Group 1

Objective: To compare between luteal phase clomiphene citrate and second cycle day clomiphene citrate on the thickness of the endometrium and clinical pregnancy rates in women with polycystic ovary syndrome. Methods: a prospective observational study conducted on 196 women with Polycystic ovary syndrome divided into two groups: Group 1 (98 patients) received 100mg of clomiphene citrate daily for 5 days starting on second cycle day and Group 2 (98 patients) received 100mg of clomiphene citrate daily starting in the luteal phase before onset of withdrawal bleeding for 5 days. Treatment and follow up applied for three cycles. Outcome measures were collected and analyzed and women who got pregnant were followed until 12 weeks of pregnancy. Results: no significant differences between the two groups regarding pre-ovulatory endometrial thickness (8.3mm in group 1vs 8.8mm in group 2), number of mature follicles (1.62 in group 1vs 1.57 in group 2) and mid-luteal serum progesterone levels(14.63ng/ml in group 1vs 14.9ng/ml in group 2). 34 women (35%) got pregnant in group 1 and 37 women (38%) in-group 2 and three patients had miscarriage in each group without any statistical significance. Conclusion: the present study does not support luteal clomiphene citrate over second cycle day clomiphene citrate to induce ovulation in infertile women with polycystic ovary syndrome.

Download Full-text

Use of letrozole versus clomiphene citrate combined with gonadotropins for ovulation induction in infertile women with polycystic ovary syndrome: a pilot study

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20174068 ◽

2017 ◽

Vol 6 (9) ◽

pp. 4098 ◽

Cited By ~ 1

Author(s):

Amitoj Athwal ◽

Ratnabali Chakravorty ◽

Dipanshu Sur ◽

Rupam Saha

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Endometrial Thickness ◽

Clomiphene Citrate ◽

Prospective Trial ◽

Serum Estradiol ◽

Ovary Syndrome ◽

Infertile Women ◽

Ovulation Stimulation ◽

Group Serum

Background: The aim of the study was to evaluate the efficacy of letrozole and clomiphene citrate (CC) in gonadotropin-combined for ovulation stimulation in women with polycystic ovary syndrome (PCOS). It was a prospective pilot study.Methods: This prospective trial included 124 patients of infertile women with PCOS. Letrozole dose of 5 mg/day (n = 65) or a CC dose of 100 mg/day (n = 59) was given on day 3 to day 7 of the menstrual cycle, combined with gonadotropin i.e. follicle stimulating hormone (FSH) at a dose 75 IU every day starting on day 7 and continued to day 9. Main outcome measures were occurrence of ovulation, number of mature follicles, serum estradiol (E2) and endometrial thicknesses on the day of human chorionic gonadotropin (hCG), and pregnancy rates.Results: The clinical profile including mean age, duration of infertility, BMI, baseline FSH, LH and E2 of patients belonging to both groups were comparable. The numbers of mature follicles (4.3±0.3 vs. 2.9±0.7) were significantly higher in letrozole+FSH group. Serum E2 levels on the day of hCG (301.78±85.7 vs. 464.7±72.9 pg/mL) were significantly lower in the letrozole+FSH group. Significant differences were found in endometrial thickness measured on the day of hCG in letrozole+FSH group (p=<0.0001). The rate of ovulation was higher in letrozole+FSH group and it was marginally statistically significant (p=0.040). The rate of pregnancy was slightly greater in the letrozole+FSH group (17.85% versus 13.33%), although not statistically significant.Conclusions: Letrozole in combination with FSH appears to be a suitable ovulation inducing agent versus CC with FSH in PCOS. This combination may be more appropriate in patients who are particularly sensitive to gonadotropin.

Download Full-text