Combined letrozole and clomiphene versus letrozole and clomiphene alone in infertile patients with polycystic ovary syndrome

Hajishafiha, M; Dehghan, Meisam; Kiarang, N; Sadegh-Asadi, Nahideh; Shayegh, Seyed Navid; Ghasemi-Rad, Mohammad

doi:10.2147/dddt.s50972

Cited by 9 publications

(6 citation statements)

References 20 publications

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“…In other studies, a combination of letrozole and gonadotropin in OI cycles resulted in more mono-ovulation and a shorter ovulation induction duration [19], in addition to a reduced incidence of multiple gestations [6]. Hajishafiha et al [16] reported five cases of twin foetuses (12%) among patients treated with gonadotropins, whereas others reported no multiple pregnancy cases following this type of treatment [17]. Multiple gestations resulted in higher risk of preterm birth and associated neonatal morbidity and expens [20].…”

Section: Discussionmentioning

confidence: 97%

“…There are a few published studies on the use of CC plus letrozole. In a study on 100 patients resistant to letrozole (four cycles) and CC (six cycles), Hajishafiha et al [16] reported a follicular development rate of 82.9% (213 of 257 cycles) in patients treated with 5 mg of letrozole plus 100 mg of CC daily for 5 D. In the same study, patients received an FSH injection on d 11 if a dominant follicle was present and received HCG trigger when the follicle was > 18 mm in size, followed by intrauterine insemination 36-38 h later. In another combination study, the patients were classified according to age and BMI and randomized to 2.5 mg of letrozole (n = 35) or combination treatment with 2.5 mg of letrozole and 50 mg of CC (n = 35) daily for 3-7 [17].…”

Section: Discussionmentioning

confidence: 99%

“…In the studies by Hajishafiha et al [16] and Mejia et al [17], 100 mg of CC plus 5 mg of letrozole and 50 mg of CC plus 2.5 mg of letrozole were administered for 5 days, respectively. In the present study, the patients received a combination of 2.5 mg of letrozole for 3 days (days of menstruation 5-7) and 100 mg of CC for 5 days (days of menstruation 3-7 mg) for one treatment cycle.…”

Section: Discussionmentioning

confidence: 99%

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A comparison between a combination of letrozole and clomiphene citrate versus gonadotropins for ovulation induction in infertile patients with clomiphene citrateresistant polycystic ovary syndrome — a retrospective study

et al. 2020

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Objectives:The aim of this study was to compare a combination treatment with CC plus letrozole versus gonadotropins in CC-resistant polycystic ovary syndrome (PCOS) patients with regard to ovulation and clinical pregnancy rate. Material and methods:One hundred sixteen CC-resistant infertile PCOS patients were evaluated retrospectively. The patients were divided into two groups. Group 1 (n = 73) received CC plus letrozole, and Group 2 (n = 43) received gonadotropins. Results:The ovulation rate in Group 1 was 65/73 (89%), the pregnancy rate was 13/73 (18%), the twin foetuses rate was 1/73 (1.3%) and the miscarriage rate was 2/73 (2.7%). In Group 2, the ovulation rate was 41/43 (95%), and the pregnancy rate was 8/43 (19%) the rate of the twin foetuses was 1/43 (2.3%) and the miscarriage rate was 1/43 (2.3%). There was no statistically significant difference in the ovulation (p = 0.25), pregnancy (p = 0.91), twin foetuses (p = 0.89) and miscarriage p = 0.89) rates between two groups.Conclusions: This new drug combination suggests that it may be a lower cost, lower risk alternative treatment that increases the rate of ovulation. Larger randomized clinical trials are needed to provide information on live birth rates of this combination.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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A comparison between a combination of letrozole and clomiphene citrate versus gonadotropins for ovulation induction in infertile patients with clomiphene citrateresistant polycystic ovary syndrome — a retrospective study

et al. 2020

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“…Hajishafiha et al conducted a population-based survey on 100 patients of infertility who failed to ovulate alone with clomiphene citrate and letrozole as monotherapy, these patients underwent 257 cycles of a combination of letrozole and clomiphene in which 213 were able to form dominant follicle (82.9%), and 44 were unable to do so (17.1%) [ 15 ]. The mean endometrial thickness on the day of human chorionic gonadotropin administration was 8.17 ±1.3 mm and the pregnancy rate was 42%.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Fertility Outcomes Following Combined Clomiphene and Letrozole Versus Letrozole Therapy for the Treatment of Polycystic Ovarian Syndrome Subfertility

Sharma¹,

Chandra²,

Sarkar³

et al. 2023

Cureus

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Background: Poly Cystic Ovarian Syndrome (PCOS) affects 8-13% of women in their reproductive age and is one of the foremost causes of female subfertility. Traditionally, clomiphene citrate has been the first-line treatment for ovulation induction in PCOS. However, the European Society of Human Reproduction and Embryology (ESHRE) international evidence-based guidelines in 2018 recommended the use of letrozole as first-line therapy for ovulation induction in anovulatory PCOS women, due to better pregnancy and live birth rates. Here we aimed to evaluate the effect of combined - clomiphene and letrozole versus letrozole for the treatment of PCOS subfertility. Methods: It was a retrospective cohort study conducted on reproductive-age women fulfilling Rotterdam Criteria for PCOS with a history of subfertility. All participants receiving at least one cycle of letrozole and clomiphene combination were recruited as cases. However, women receiving letrozole only for ovulation induction were taken as controls. Hospital records were abstracted for data on baseline characteristics such as age, duration of infertility, PCOS phenotype, body mass index (BMI), past medical and fertility history, treatment with ovulation induction agents, and metformin use. The mean size of the largest follicle, number of dominant follicles of size greater than 15 mm and endometrial thickness on Days 12-14 or on the day of the luteinizing hormone (LH) surge were recorded. A cycle was termed ovulatory if serum progesterone levels were > 5.0 ng/ml on the seventh day after the LH surge or day 22 in the absence of the LH surge. Data pertaining to therapy-associated side effects were also abstracted from the clinical records. Results: Amongst the ovulatory cycles in both groups, there was no significant difference in the day of the LH surge. Serum progesterone levels on the seventh day post-ovulation were higher with combination therapy (19.35 v/s 26.71, p=0.004). The number of ovulatory cycles was also greater with combination therapy, but the difference was just short of significant (25 vs 18, p=0.08). The mean diameter of the largest follicle, incidence of multi-follicular ovulation, and thin endometrium were similar in both groups. The adverse effect profile was similar in both groups. Conclusion: Combination treatment of clomiphene citrate with letrozole may potentially improve fertility outcomes in PCOS subfertility in terms of the likelihood of ovulation and higher post-ovulatory progesterone levels, however, larger studies are required.

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“…23 using letrozole (5 mg) and CC (100 mg) daily for 5 days with an injection of FSH on day 11 in participants who were shown to be resistant to letrozole and CC. 22 However, the methodology of this study was limited in that it took follicular development instead of a valid measure of ovulation as the outcome measure and was conducted without randomization and in a limited population of women with PCOS resistant to single drug treatment of both CC and letrozole.…”

Section: Discussionmentioning

confidence: 99%

A triple‐blind, randomized controlled trial, comparing combined letrozole and clomiphene versus only letrozole for ovulation induction in women with polycystic ovarian syndrome

Panda

Sharmila

Kalidoss

et al. 2022

Intl J Gynecology & Obste

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Polycystic ovary syndrome (PCOS) is considered one of the most common causes of anovulatory infertility and has a varied prevalence. While worldwide data show a prevalence of 5.5% to 12.6%, Indian data show a prevalence ranging between 8.2% and 22.5%. [1][2][3] Clomiphene citrate (CC), a commonly used ovulation-inducing agent, inhibits the negative feedback of estrogen, resulting in increased secretion of gonadotropins thus inducing follicular development. 4,5 Over the past decade, letrozole has become a popular oral ovulation induction agent. It works by inhibiting the aromatase enzyme and thus prevents the androgen from being converted into estrogen. There is increased sensitivity to follicle-stimulating hormone (FSH) leading to a transient increase in intraovarian androgens, which is thought to be associated with better ovulatory rates of letrozole. 6 Because of the varied mechanisms of action, it has been hypothesized that combining letrozole and CC may provide a higher rate of ovulation. Thus, this combination therapy could be a potential option for ovulation induction in women with PCOS to avoid unnecessary use of gonadotropins. Given the scarce data in

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Combined letrozole and clomiphene versus letrozole and clomiphene alone in infertile patients with polycystic ovary syndrome

Cited by 9 publications

References 20 publications

A comparison between a combination of letrozole and clomiphene citrate versus gonadotropins for ovulation induction in infertile patients with clomiphene citrateresistant polycystic ovary syndrome — a retrospective study

A comparison between a combination of letrozole and clomiphene citrate versus gonadotropins for ovulation induction in infertile patients with clomiphene citrateresistant polycystic ovary syndrome — a retrospective study

Assessment of Fertility Outcomes Following Combined Clomiphene and Letrozole Versus Letrozole Therapy for the Treatment of Polycystic Ovarian Syndrome Subfertility

A triple‐blind, randomized controlled trial, comparing combined letrozole and clomiphene versus only letrozole for ovulation induction in women with polycystic ovarian syndrome

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