Randomized controlled trial comparing letrozole with laparoscopic ovarian drilling in women with clomiphene citrate-resistant polycystic ovary syndrome

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Abstract

The aim of the present study was to compare the reproductive outcomes of letrozole and laparoscopic ovarian drilling (LOD) in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). A total of 141 women with CC-resistant PCOS were enrolled and randomly allocated into groups A and B. Group A (n=71) received 2.5 mg letrozole from days 5 to 10 of menses for up to six cycles, and group B (n=70) underwent LOD. A 6-month follow-up was performed. No statistically significant difference was found in the baseline clinical characteristics and the major serum hormone profiles, including luteinizing hormone, follicle-stimulating hormone, estradiol and free testosterone, between the two groups. Women receiving letrozole had a lower rate of spontaneous abortion (6.9 vs. 15.8%) and higher clinical pregnancy (40.8 vs. 27.1%) and live birth (38.0 vs. 22.9%) rates; however, the differences were not statistically significant. Letrozole had superior reproductive outcomes compared with LOD in women with CC-resistant PCOS; therefore, letrozole could be used as the first-line treatment for women with CC-resistant PCOS.

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Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome.

Michael Steinkampf, G Gosman-Hedström, Maria A Cataldo … (2007)

The polycystic ovary syndrome is a common cause of infertility. Clomiphene and insulin sensitizers are used alone and in combination to induce ovulation, but it is unknown whether one approach is superior. We randomly assigned 626 infertile women with the polycystic ovary syndrome to receive clomiphene citrate plus placebo, extended-release metformin plus placebo, or a combination of metformin and clomiphene for up to 6 months. Medication was discontinued when pregnancy was confirmed, and subjects were followed until delivery. The live-birth rate was 22.5% (47 of 209 subjects) in the clomiphene group, 7.2% (15 of 208) in the metformin group, and 26.8% (56 of 209) in the combination-therapy group (P<0.001 for metformin vs. both clomiphene and combination therapy; P=0.31 for clomiphene vs. combination therapy). Among pregnancies, the rate of multiple pregnancy was 6.0% in the clomiphene group, 0% in the metformin group, and 3.1% in the combination-therapy group. The rates of first-trimester pregnancy loss did not differ significantly among the groups. However, the conception rate among subjects who ovulated was significantly lower in the metformin group (21.7%) than in either the clomiphene group (39.5%, P=0.002) or the combination-therapy group (46.0%, P<0.001). With the exception of pregnancy complications, adverse-event rates were similar in all groups, though gastrointestinal side effects were more frequent, and vasomotor and ovulatory symptoms less frequent, in the metformin group than in the clomiphene group. Clomiphene is superior to metformin in achieving live birth in infertile women with the polycystic ovary syndrome, although multiple birth is a complication. (ClinicalTrials.gov number, NCT00068861 [ClinicalTrials.gov].). Copyright 2007 Massachusetts Medical Society.

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Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate.

Mohamed Mitwally, Robert F. Casper (2001)

To use aromatase inhibition for induction of ovulation in women in whom clomiphene citrate (CC) treatment was unsuccessful. Prospective trial in infertility patients treated with CC. Two tertiary-referral infertility clinics associated with the Division of Reproductive Sciences, University of Toronto. Twelve patients with anovulatory polycystic ovary syndrome (PCOS) and 10 patients with ovulatory infertility, all of whom had previously received CC with an inadequate outcome (no ovulation and/or endometrial thickness of < or =0.5 cm). The aromatase inhibitor letrozole was given orally in a dose of 2.5 mg on days 3-7 after menses. Occurrence of ovulation, endometrial thickness, and pregnancy rates. With CC treatment in patients with PCOS, ovulation occurred in 8 of 18 cycles (44.4%), and all ovulatory cycles for the women included in this study had endometrial thickness of < or =0.5 cm. In 10 ovulatory patients, 15 CC cycles resulted in a mean number of 2.5 mature follicles, but all cycles had endometrial thickness of < or =0.5 cm on the day of hCG administration. With letrozole treatment in the same patients with PCOS, ovulation occurred in 9 of 12 cycles (75%) and pregnancy was achieved in 3 patients (25%). In the 10 patients with ovulatory infertility, letrozole treatment resulted in a mean number of 2.3 mature follicles and mean endometrial thickness of 0.8 cm. Pregnancy was achieved in 1 patient (10%). Oral administration of the aromatase inhibitor letrozole is effective for ovulation induction in anovulatory infertility and for increased follicle recruitment in ovulatory infertility. Letrozole appears to avoid the unfavorable effects on the endometrium frequently seen with antiestrogen use for ovulation induction.

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Androgens promote oocyte insulin-like growth factor I expression and initiation of follicle development in the primate ovary.

Jing-Wen Wang, J. Zhou, Stephen Bondy … (1999)

In the study reported here, we investigated the effect of androgens on recruitment of resting, primordial follicles into the actively growing pool. Healthy, random-cycling female rhesus monkeys were treated with testosterone, dihydrotestosterone (DHT), or vehicle for 3-10 days, after which ovaries were collected for histological analysis. The first stage of follicle growth is the formation of the primary follicle, consisting of an oocyte surrounded by a single layer of cuboidal granulosa cells. The number of primary follicles was significantly increased over time in testosterone-treated animals. In situ hybridization showed that androgen treatment resulted in an increase to 3-fold in insulin-like growth factor I (IGF-I) and to 5-fold in IGF-I receptor mRNA in primordial follicle oocytes. DHT effects were comparable to those of testosterone, showing that these are androgen receptor-mediated phenomena. These data show that androgens promote initiation of primordial follicle growth and implicate oocyte-derived IGF-I in this activation process.

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Author and article information

Journal

Journal ID (nlm-ta): Exp Ther Med

Journal ID (iso-abbrev): Exp Ther Med

Journal ID (publisher-id): ETM

Title: Experimental and Therapeutic Medicine

Publisher: D.A. Spandidos

ISSN (Print): 1792-0981

ISSN (Electronic): 1792-1015

Publication date (Print): October 2015

Publication date (Electronic): 19 August 2015

Publication date PMC-release: 19 August 2015

Volume: 10

Issue: 4

Pages: 1297-1302

Affiliations

[1 ]Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, P.R. China

[2 ]Department of Obstetrics and Gynecology, Central South University Affiliated to Xiang Ya Hospital of Reproductive Center, Changsha, Hunan 410008, P.R. China

[3 ]Translational Center for Stem Cell Research, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, P.R. China

Author notes

Correspondence to: Dr Yazhong Ji, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Shanghai 200065, P.R. China, E-mail: jiyazhong@ 123456hotmail.com

Dr Yumei Li, Department of Obstetrics and Gynecology, Central South University Affiliated to Xiang Ya Hospital of Reproductive Center, 87 Xiangya Road, Changsha, Hunan 410008, P.R. China, E-mail: liyumei19800425@ 123456yeah.net

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Contributed equally

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Publisher ID: ETM-0-0-2690

DOI: 10.3892/etm.2015.2690

PMC ID: 4578114

PubMed ID: 26622481

SO-VID: d43c4a27-b81e-447b-a0b1-8d3ee9150270

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This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 4.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

Randomized controlled trial comparing letrozole with laparoscopic ovarian drilling in women with clomiphene citrate-resistant polycystic ovary syndrome

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Most cited references 25

Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome.

Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate.

Androgens promote oocyte insulin-like growth factor I expression and initiation of follicle development in the primate ovary.

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