1. Introduction

Polycystic ovarian syndrome (PCOS) is a group of heterogeneous endocrine disease affecting women characterized by irregular menses, hyperandrogenism, and polycystic ovaries. The diagnoses of polycystic ovarian syndrome are frequently made for the first time in the infertility clinic during evaluations for infertility. Infertility is the main clinical manifestation of

© 2018 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and eproduction in any medium, provided the original work is properly cited.

ovulatory dysfunction in patients with PCOS. The prevalence is between 8.5 and 20% depending on the criteria used for the identification of the condition [1, 2].

The American societies studying PCOS indicate that weight loss is a primary therapy in PCOS. That weight loss as little as 5–10% of body weight can regularize menses and improve

Ovulation Induction in Women with Polycystic Ovary Syndrome: What is the Optimal Option?

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In many countries, lifestyle intervention is recommended as this has led to higher spontaneous

Weight reduction through dietary modification and exercise is recommended for overweight PCOS patient [22]. Some studies show that over 10% of women with PCOS will regain spontaneous ovulation when placed on low calorie, low-fat diet, and exercise or with surgery. The aim of dietary restriction and exercise is toward losing about 5–10% of their body weight. This form of treatment alone or in combination with pharmacologic agents would reduce insulin resistance and is advocated for overweight to obese women of BMI > 24 [22]. The drawbacks of this method of treatment are that such women lack the motivation to remain on diet and exercise, and may not be able to achieve the desired weight loss to trigger spontaneous ovulation, and most times pharmacologic agents are added to assist ovulation. The duration it takes to achieve the desired body weight to bring about ovulation is not defined, but differs among patients. Other drawbacks are that it may not treat anovulation in normal-weight women even though they also have insulin resistance as well. The advantage is that it is cost-effective and will not produce any form of drug reactions. It will also reduce the high level of luteinizing hormone and reduce early pregnancy loss. A combination of lifestyle modification with weight loss before pharmacologic ovulation-inducing agents improved ovulation and live birth in women with PCOS in a USA study [23] and in addition, required lower doses of pharmacologic agent for ovulation induction.

Several pharmacologic agents have been used to induce ovulation in these patients. They have achieved varied success with attendant setbacks from these drugs especially in achieving pregnancy and with adverse pregnancy outcomes. These drugs include clomiphene citrate,

Clomiphene citrate is traditionally the first-line drug used to induce ovulation in women with anovulation due to PCOS [2]. This drug has both estrogenic agonist and antagonist effects. It produces its effect principally by blocking the estrogen receptors in the hypothalamus to increase the endogenous follicle-stimulating hormone (FSH) to bring about folliculogenesis and ovulation. Clomiphene citrate when compared to other pharmacologic agents used for induction have been found to be inferior to drugs like letrozole, or a combination of clomiphene citrate and metformin with respect to ovulation, pregnancy, or live birth [6]. Clomiphene citrate in combination with metformin showed a higher pregnancy rate than clomiphene citrate alone or metformin alone. The odds ratio for pregnancy when clomiphene citrate in combination with metformin is compared to clomiphene citrate alone is 1.8 (1.35–2.42) indicating that clomiphene

response to ovulation induction and fertility medications [9, 12].

3. Pharmacologic agents and ovulation induction

3.1. Use of pharmacologic agents in induction of ovulation

metformin, letrozole, gonadotropins, inositol, and tamoxifen.

3.1.1. Clomiphene citrate

ovulation rates and natural conception rates [20, 21].

Anovulation is a cause of infertility in up to a quarter of all cases of infertility. Normogonadotropic anovulation classified as World Health Organization (WHO) group II is the most common category of anovulatory infertility. PCOS is the most common in this group and notably the commonest endocrine disorder and cause of anovulation [1–3]. Insulin resistance is implicated in the ovulatory dysfunction in PCOS by disrupting the hypothalamo-pituitaryovarian axis. Insulin resistance also leads to other comorbidities such as metabolic syndrome, hypertension, dyslipidemia, glucose intolerance, and diabetes mellitus as well as mental disorders such as depression, anxiety, bipolar disorders and binge eating [1, 4]. Women with PCOS present to the fertility clinic with chronic oligo/anovulation and hyperandrogenism, with attendant negative effects on their fertility. The desire to reproduce is very intense in many communities where there is high premium placed on reproduction as a means of survival. So, these women having learnt the diagnosis of their conditions are very expectant that their conditions will soon be reversed following treatment such that they could ovulate, become pregnant, and successfully have children. Many a times, the drug to bring about the reversal of anovulation refuses to work due to innate characteristics within the woman, the drug, or even the environment. This challenge has led to the development and use of several different pharmacologic agents used singularly and in combination to deal with the challenge of anovulation. Other physical methods and herbal preparations have also been deployed to varying degree of success to combat anovulation in women with PCOS.

Central to the management of women with infertility from PCOS is the induction of ovulation. The treatment options for infertility in women with PCOS include clomiphene citrate, gonadotropins, laparoscopic ovarian drilling (LOD), and assisted reproductive technology [1, 5]. Common to all methods is the induction of ovulation. Letrozole and metformin also play important roles in ovulation induction as has been now well demonstrated. The use of these pharmacologic agents has been shown to be superior to placebo or no treatment in terms of pregnancy or ovulation [6].
