Comparison Between Two Ovulation Induction Therapies and LOD on Clinical Outcomes in CC-Resistant PCOS Women

Summary

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting 4-8% of reproductive-aged women and is a leading cause of infertility due to oligo-anovulation (1). Studies suggest a higher prevalence of 17.8-19.9% based on Rotterdam diagnostic criteria. PCOS is diagnosed by the presence of at least two out of three criteria: oligo- and/or anovulation, hyperandrogenism, and polycystic ovaries, with other etiologies excluded (2). Clomiphene citrate (CC), a selective estrogen receptor modulator, has been the first-line treatment for inducing ovulation in anovulatory women with PCOS for decades. Approximately 80% of women resume ovulation with CC, but only 35-40% achieve pregnancy. About 15-40% of women are resistant to CC, defined as failure to ovulate after receiving a maximum dosage of 150 mg per day for 5 days starting on the third day of the menstrual cycle. For CC-resistant women, metformin, an insulin sensitizer, has been explored but shows limited effectiveness except in combination with CC. Gonadotropins are the standard treatment for CC-resistant PCOS but come with risks of multiple pregnancies and ovarian hyperstimulation syndrome (OHSS) (3). Letrozole, an aromatase inhibitor, is another treatment option that prevents the conversion of androgens to estrogen, thereby increasing gonadotropin-releasing hormone (GnRH) secretion and promoting ovulation. Letrozole has shown superior ovulation and live birth rates compared to CC and is now recommended as the first-line treatment for anovulation in women with PCOS. It has comparable rates of OHSS and miscarriage to CC, but fewer relevant studies have compared it directly to laparoscopic ovarian drilling (LOD) (4). LOD is an alternative to gonadotropins for inducing ovulation in CC-resistant PCOS. It involves surgical intervention, which can be either unilateral or bilateral, and is effective without the risks of multiple pregnancies or OHSS. LOD also increases ovarian responsiveness to CC. Despite minimal morbidity, LOD can lead to tubo-ovarian adhesions and premature ovarian failure, although these risks are reduced by careful technique (5).

Timeline

Start

2020-01-01

Primary completion

2024-01-01

Completion

2024-01-31

Publications

• Results Thomas S, Woo I, Ho J, Jones T, Paulson R, Chung K, Bendikson K. Ovulation rates in a stair-step protocol with Letrozole vs clomiphene citrate in patients with polycystic ovarian syndrome. Contracept Reprod Med. 2019 Dec 9;4:20. doi: 10.1186/s40834-019-0102-4. eCollection 2019.
• Results Yildiz BO, Bozdag G, Yapici Z, Esinler I, Yarali H. Prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria. Hum Reprod. 2012 Oct;27(10):3067-73. doi: 10.1093/humrep/des232. Epub 2012 Jul 9.
• Results Brown J, Farquhar C. Clomiphene and other antioestrogens for ovulation induction in polycystic ovarian syndrome. Cochrane Database Syst Rev. 2016 Dec 15;12(12):CD002249. doi: 10.1002/14651858.CD002249.pub5.
• Results Yang AM, Cui N, Sun YF, Hao GM. Letrozole for Female Infertility. Front Endocrinol (Lausanne). 2021 Jun 16;12:676133. doi: 10.3389/fendo.2021.676133. eCollection 2021.
• Results Liu W, Dong S, Li Y, Shi L, Zhou W, Liu Y, Liu J, Ji Y. Randomized controlled trial comparing letrozole with laparoscopic ovarian drilling in women with clomiphene citrate-resistant polycystic ovary syndrome. Exp Ther Med. 2015 Oct;10(4):1297-1302. doi: 10.3892/etm.2015.2690. Epub 2015 Aug 19.
• Results Moazami Goudarzi Z, Fallahzadeh H, Aflatoonian A, Mirzaei M. Laparoscopic ovarian electrocautery versus gonadotropin therapy in infertile women with clomiphene citrate-resistant polycystic ovary syndrome: A systematic review and meta-analysis. Iran J Reprod Med. 2014 Aug;12(8):531-8.
• Results Davar R, Tabibnejad N, Kalantar SM, Sheikhha MH. The luteinizing hormone beta-subunit exon 3 (Gly102Ser) gene mutation and ovarian responses to controlled ovarian hyperstimulation. Iran J Reprod Med. 2014 Oct;12(10):667-72.
• Results Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod. 2008 Mar;23(3):462-77. doi: 10.1093/humrep/dem426.
• Results Godinjak Z, Javoric R. Clinical outcome and hormone profiles before and after laparoscopic electroincision of the ovaries in women with polycystic ovary syndrome. Bosn J Basic Med Sci. 2007 May;7(2):171-5. doi: 10.17305/bjbms.2007.3076.
• Results Abu Hashim H, Al-Inany H, De Vos M, Tournaye H. Three decades after Gjonnaess's laparoscopic ovarian drilling for treatment of PCOS; what do we know? An evidence-based approach. Arch Gynecol Obstet. 2013 Aug;288(2):409-22. doi: 10.1007/s00404-013-2808-x. Epub 2013 Mar 30.
• Results Ibrahim MH, Tawfic M, Hassan MM, Sedky OH. Letrozole versus laparoscopic ovarian drilling in infertile women with PCOS resistant to clomiphene citrate. Middle East Fertility Society Journal. 2017 Dec 1;22(4):251-4.
• Results Abdellah MS. Reproductive outcome after letrozole versus laparoscopic ovarian drilling for clomiphene-resistant polycystic ovary syndrome. Int J Gynaecol Obstet. 2011 Jun;113(3):218-21. doi: 10.1016/j.ijgo.2010.11.026. Epub 2011 Apr 1.
• Results Elnashar A, Abdelmageed E, Fayed M, Sharaf M. Clomiphene citrate and dexamethazone in treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective placebo-controlled study. Hum Reprod. 2006 Jul;21(7):1805-8. doi: 10.1093/humrep/del053. Epub 2006 Mar 16.
• Results Yadav P, Singh S, Singh R, Jain M, Awasthi S, Raj P. To study the effect on fertility outcome by gonadotropins vs laparoscopic ovarian drilling in clomiphene-resistant cases of polycystic ovarian syndrome. Journal of the South Asian Federation of Obstetrics and Gynaecology. 2017 Oct;9(4):336-40.
• Results Mehrabian F, Eessaei F. The laparoscopic ovarian electrocautery versus gonadotropin therapy in infertile women with clomiphene citrate-resistant polycystic ovary syndrome; a randomized controlled trial. J Pak Med Assoc. 2012 Mar;62(3 Suppl 2):S42-4.
• Results Ganesh A, Goswami SK, Chattopadhyay R, Chaudhury K, Chakravarty B. Comparison of letrozole with continuous gonadotropins and clomiphene-gonadotropin combination for ovulation induction in 1387 PCOS women after clomiphene citrate failure: a randomized prospective clinical trial. J Assist Reprod Genet. 2009 Jan;26(1):19-24. doi: 10.1007/s10815-008-9284-4. Epub 2009 Jan 7.

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