Ovarian drilling for surgical treatment of polycystic ovarian syndrome: a comprehensive review

This systematic literature review is intended to clarify and evaluate the results obtained by ovarian drilling as surgical treatment for polycystic ovarian syndrome (PCOS). Four databases were consulted (Medline at the National Library of Medicine, USA; Cochrane Library, UK; National Guideline Clearinghouse, USA; and the Health Technology Assessment Database, Sweden) and searched for 'polycystic ovary syndrome' plus 'drilling' in the title or abstract. The assessment criteria used to define the efficacy of the procedure were the rates of ovulation, clinical pregnancy and early miscarriage. Alternatives to surgical ovarian drilling were evaluated. This search produced 147 references, 81 of which met the selection criteria. This review of infertility management in women with PCOS indicates that ovarian drilling is a second-line treatment when treatment with clomiphene citrate fails to lead to conception. The benefits of ovarian drilling are that it does not induce either hyperstimulation syndrome or multiple pregnancies. It is concluded that ovarian drilling is an option in the management of female infertility associated with PCOS, especially as a second-line treatment after the failure of clomiphene citrate treatment.     

The treatment of infertility in polycystic ovary syndrome: a brief update

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. Lifestyle change alone is considered the first-line treatment for the management of infertile anovulatory PCOS women who are overweight or obese. First-line medical ovulation induction therapy to improve fertility outcomes is clomiphene citrate, whilst gonadotrophins, laparoscopic ovarian surgery or possibly metformin are second line in clomiphene citrate-resistant PCOS women. There is currently insufficient evidence to recommend aromatase inhibitors over that of clomiphene citrate in infertile anovulatory PCOS women in general or specifically in therapy naive or clomiphene citrate-resistant PCOS women. IVF/ICSI treatment is recommended either as a third-line treatment or in the presence of other infertility factors.     

Ovulation induction management of PCOS

Ovulation induction is the principal infertility treatment for women with polycystic ovarian syndrome (PCOS). Among PCOS patients who are overweight or obese, weight loss is the most physiologic method of inducing ovulation. For women in whom weight loss is not possible, or for lean women with PCOS, clomiphene citrate is an effective first-line method of ovulation induction. In clomiphene-resistant women, alternative treatments include adjunctive metformin or dexamethasone, aromatase inhibitors, or ovarian drilling. If there is no pregnancy despite several cycles of successful ovulation induction, gonadotropin treatment should be considered, in which case in vitro fertilization is recommended as the safest and most effective strategy.     

Primum Non Nocere

Surgical ovarian wedge resection was the first established treatment for women with anovulatory polycystic ovary syndrome (PCOS) but was largely abandoned both due to the risk of postsurgical adhesions and the introduction of medical ovulation induction. Laparoscopic ovarian drilling (LOD) is an alternative method to induce ovulation in PCOS patients with clomiphene citrate resistance instead of gonadotropins. Surgical therapy with LOD may avoid or reduce the need for gonadotropins or may facilitate their use. However, the procedure, though effective, can be traumatic on the ovaries, which may cause postoperative adhesions and/or diminished ovarian reserve. In over-enthusiastic hands, this day-care procedure might lead to iatrogenic premature ovarian failure in young women. Some trials have compared LOD with gonadotropins, but, because of variations in study design and small sample size, the results are inconsistent and definitive conclusions about the relative efficacy of LOD and gonadotropins cannot be extracted from the individual studies. Today, evidence-based reviews conclude that there is no evidence of a significant difference in rates of clinical pregnancy, live birth or miscarriage in women with clomiphene-resistant PCOS undergoing LOD compared to other medical treatments. The reduction in multiple pregnancy rates in women undergoing LOD is the only pro-LOD argument. However, there are ongoing serious concerns about the long-term effects of LOD on ovarian function.     

Therapeutic strategies for ovulation induction in infertile women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by hirsutism, obesity, hyperandrogenism and insulin resistance. The syndrome is often accompanied by infertility because of anovulation. Many approaches have been proposed to solve this problem, with the most commonly used therapies being ovarian drilling and pharmacological ovulation induction. Ovarian drilling is a procedure in which a laser fiber or electro-surgical needle punctures the ovary four to ten times. Side-effects are rare and often related to surgery itself. Pharmacological strategies include administration of metformin and insulin-sensitizing agents, clomiphene citrate (CC), gonadotropins and aromatase inhibitors. Metformin appears valuable in increasing ovulation rate, menstrual cyclicity and pregnancy rate. CC is an oral estrogen antagonist that raises circulating concentrations of follicle-stimulating hormone (FSH) and induces follicular growth in most women with PCOS and anovulation. Failure to respond is associated with high body mass index and high androgen levels. Aromatase inhibitors mimic the central reduction of negative feedback through which CC works. Ovulation induction with recombinant FSH has proved successful, but treatment requires skill and experience to avoid multiple pregnancies and ovarian hyperstimulation syndrome. The hypothetical deleterious effects of the high luteinizing hormone concentrations observed in PCOS patients seem to be related to the concomitant hyperinsulinemia (and/or insulin resistance). A thorough understanding of the syndrome and a careful assessment of each patient are the mainstays for choosing an appropriate treatment regimen.     

GnRH antagonists for treatment of polycystic ovarian syndrome

To review treatment options for women with polycystic ovary syndrome (PCOS) seeking relief from infertility. Review article and case studies. Treatment options for women with PCOS include lifestyle modification, treatment with insulin-sensitizing agents, ovulation induction with clomiphene citrate (CC), FSH preparations, and possibly, GnRH antagonists. The GnRH antagonists provide a new treatment option for women with PCOS. When the goal is to restore normal ovulation, the use of GnRH antagonists is limited to the prevention of LH surges. When undertaking controlled ovarian hyperstimulation (COH) in women with PCOS, a GnRH antagonist protocol should be the protocol of choice.     

Surgical treatment in polycystic ovary syndrome

PURPOSE OF REVIEW: The purpose of this review is to provide a critical summary of current knowledge on the role and effectiveness of ovarian surgery in the treatment of polycystic ovary syndrome. RECENT FINDINGS: Clomiphene citrate is used as a first-line treatment for ovulation induction in infertile anovulatory patients with polycystic ovary syndrome. In clomiphene citrate-resistant women, other treatment modalities such as laparoscopic electrocautery or ovulation induction with gonadotropins have been proposed as alternative therapies. Although gonadotropin treatment and laparoscopic ovarian drilling have demonstrated similar reproductive outcomes, laparoscopic ovarian drilling has some advantages over gonadotropin treatment such as lower cost per pregnancy, improvement in menstrual regularity, and better long-term reproductive performance. On the other hand, knowledge about the pathogenesis of polycystic ovary syndrome has been growing and insulin-sensitizing drugs have gained popularity as a new treatment option. SUMMARY: According to current data, metformin has gained popularity as first-line management in clomiphene citrate-resistant women with polycystic ovary syndrome. If ovulation does not occur within several months after treatment with metformin, after the evaluation of all pros and cons related to each treatment, laparoscopic ovarian drilling or gonadotropins may be considered as an effective option according to patient choice.     

Sterilitätsbehandlung bei Patientinnen mit polyzystischem Ovarsyndrom (PCOS)

The treatment of infertility in patients with polycystic ovary syndrome (PCOS) is based on two main principles: restoration of endogenous ovulatory cycles or direct ovarian stimulation. Treatment with corticoids or oral contraceptives is no longer a sufficient option. Ovarian electrocautery leads to ovulatory cycles in about 80%. Besides clomiphene stimulation, step-up or step-down protocols with gonadotropins, in particular follicle-stimulating hormone (FSH), are the protocols of choice. The addition of gonadotropin-releasing hormone (GnRH) analogues did not further improve the stimulation outcome. Modern concepts involve the medical correction of hyperinsulinemia by insulin-sensitizing drugs, in particular metformin. Metformin can lead to spontaneous ovulatory cycles and improves the ovarian response to clomiphene and FSH. In the future, combinations of ovarian stimulation and drugs that improve ovarian response will be the treatment options of choice.     

Effects of myo-inositol in women with PCOS: a systematic review of randomized controlled trials

Polycystic ovary syndrome (PCOS) affects 5%–10% of women in reproductive age, and it is the most common cause of infertility due to ovarian dysfunction and menstrual irregularity. Several studies have reported that insulin resistance is common in PCOS women, regardless of the body mass index. The importance of insulin resistance in PCOS is also suggested by the fact that insulin-sensitizing compounds have been proposed as putative treatments to solve the hyperinsulinemia-induced dysfunction of ovarian response to endogenous gonadotropins. Rescuing the ovarian response to endogenous gonadotropins reduces hyperandrogenemia and re-establishes menstrual cyclicity and ovulation, increasing the chance of a spontaneous pregnancy. Among the insulin-sensitizing compounds, there is myo-inosiol (MYO). Previous studies have demonstrated that MYO is capable of restoring spontaneous ovarian activity, and consequently fertility, in most patients with PCOS. With the present review, we aim to provide an overview on the clinical outcomes of the MYO use as a treatment to improve ovarian function and metabolic and hormonal parameters in women with PCOS.     

Laparoscopic ovarian drilling as first line of treatment in infertile women with polycystic ovary syndrome.

Laparoscopic ovarian drilling (LOD) is used as a first line of treatment, as a second line of treatment after patients have proved resistant to clomiphene or as a third line of treatment after failed ovulation induction with gonadotropins. We present the postoperative pregnancy rates of 57 women to evaluate a potential optimal time of LOD together with the other treatment regimens of infertile women with polycystic ovary syndrome (PCOS). Data on the preoperative and operative treatment, and background data were evaluated for their influence on pregnancy rates. The pregnancy rate was 61% among women with PCOS who had LOD. No difference was found in the clinical data between the women who became pregnant and those who did not. Likewise, no difference was found between the women who had pre- and/or postoperative medical ovulation treatment and those who had none. The median time to pregnancy after LOD was 135 days. LOD alone resolves infertility within 4-6 months in 50-60% of couples. A strategy with diagnostic laparoscopy and LOD as the first line of treatment of infertility in women with PCOS will shorten the time to pregnancy for many women, reduce the need for medical ovulation induction and enable diagnosis of those women with anatomic infertility, who can achieve pregnancy only by in vitro fertilization treatment.     

Ovulatory disorders and infertility

Ovulatory disorders represent a major cause of infertility. The World Health Organization classification offers a useful frame for diagnosis and treatment. Polycystic ovary syndrome (PCOS) is the most common cause of oligoovulation and anovulation. Treatment of infertility associated with PCOS has changed in the last decade due to the introduction of new medications. Insulin-sensitizing drugs, such as metformin, became an integral part of treatment. Aromatase inhibitors will most probably replace clomiphene citrate in the future. Women who fail to ovulate or conceive after first-line treatment options are often referred for gonadotropin treatment. Laparoscopic ovarian drilling, which has been evaluated in well-designed trials, may be an alternative to gonadotropins. In vitro fertilization, which yields high pregnancy rates, is the final treatment option when all else fails. Hypogonadotropic anovulation is treated with exogenous gonadotropins, and little has changed in its management. Women with hypergonadotropic hypogonadism should be counseled for adoption or in vitro fertilization with donated oocytes as spontaneous and treatment-associated pregnancy rates are very low.     

Polycystic Ovary Syndrome: Fertility Management

Polycystic ovary syndrome (PCOS) is characterized by a series of symptoms, including oligomenorrhea or amenorrhea anovulation or infertility; it is associated with insulin resistance and compensatory hyperinsulinemia. Several treatment options are available for women with anovulatory infertility related to PCOS. Clomiphene citrate (CC) is the first-choice for induction of ovulation in PCOS patients. Laparoscopic ovarian drilling (LOD) or gonadotropin ovarian stimulation can be offered after failure of CC to achieve pregnancy. Hyperinsulinemia related to PCOS can be corrected by weight loss or insulin-sensitizing agents, such as metformin, which alone or in combination with other agents are capable of restoring ovulation. Only very limited clinical data are available on the use of letrozole at present, so letrozole cannot be recommended for routine use in ovulation induction. When all treatments fail, in vitro fertilization and embryo transfer (IVF/ET) can be tried and can have excellent results. Many treatment options available today ensure that the majority of women who are subfertile due to PCOS can be treated successfully.     

Optimizing ovulation induction in women with polycystic ovary syndrome

Recent developments in our understanding of the pathophysiology of polycystic ovary syndrome led to the introduction of new therapeutic approaches. It is apparent that a significant proportion of women with polycystic ovary syndrome have insulin resistance and compensatory hyperinsulinemia. Growing evidence indicates that elevated serum insulin induces hyperandrogenism, which in turn leads to anovulation and infertility. Hyperinsulinemia also contributes to the increased risk for cardiovascular disorders and type 2 diabetes mellitus. These concepts provide rationale for therapies focused on treatments of insulin resistance. In particular, weight loss and exercise have been shown to increase insulin sensitivity and improve ovulatory function. Metformin, an insulin-sensitizing agent, is particularly effective in women with polycystic ovary syndrome who have significant insulin resistance. Metformin use leads to a decrease in serum insulin and androgen levels as well as an improvement in ovulatory function. Moreover, it appears to ameliorate cardiovascular risk factors. Other approaches to ovulation induction in women with polycystic ovary syndrome include traditional therapies using clomiphene citrate or gonadotropins. In clomiphene-resistant subjects, one can consider laparoscopic ovarian drilling and other forms of partial ovarian resection or destruction.     

Clomiphene citrate in the twenty-first century

Clomiphene citrate is the drug most commonly prescribed for ovulation induction. It is the first choice medication in normogonadotrophic oligo/amenorrhoeic infertility (WHO group 2), essentially associated with polycystic ovaries. Anovulatory women who are responsive to clomiphene citrate should be treated for at least six cycles and the treatment should probably be limited to a maximum of 12 cycles. It is necessary to monitor at least the first cycle with ultrasonography because of the risk of multiple pregnancy and the variable response of patients to different doses of clomiphene. In addition, the risk of ovarian hyperstimulation syndrome should not be underestimated. More triplets and higher order pregnancies result from ovulation induction than from in vitro fertilization, and multiple pregnancy has many risks for both mother and babies. The role of empirical clomiphene in the treatment of unexplained infertility is debatable and the present data are inconclusive. Obesity, hyperandrogenaemia and insulin resistance are important factors in clomiphene-resistant patients. Failure to ovulate in response to clomiphene has been approached by either medical or surgical treatment. An effective alternative medical treatment is gonadotrophin injections. Treatment with metformin and the new generation of insulin-sensitizing drugs is under evaluation. The most widely used surgical treatment today is laparoscopic ovarian drilling, which appears to be as effective as gonadotrophin therapy.     

Surgical or medical treatment of polycystic ovary syndrome: a cost-benefit analysis.

With the availability of laparoscopic ovarian cautery, there has been a resurgence in interest in the surgical treatment of clomiphene citrate-resistant polycystic ovary syndrome (PCOS). Comparison of ovulation and pregnancy rates has found no difference in success rates between ovarian cautery and gonadotropin ovulation induction for such women. We have therefore compared the cost of laparoscopic ovarian cautery with that of a typical cycle of gonadotropin ovulation induction, and also found that there is little difference. Because of the potential advantages of ovarian cautery, we recommend this surgery as the next line of treatment if clomiphene citrate fails to induce ovulation in PCOS patients, before gonadotropins are introduced.     

Clomiphene citrate in the twenty-first century

Clomiphene citrate is the drug most commonly prescribed for ovulation induction. It is the first choice medication in normogonadotrophic oligo/amenorrhoeic infertility (WHO group 2), essentially associated with polycystic ovaries. Anovulatory women who are responsive to clomiphene citrate should be treated for at least six cycles and the treatment should probably be limited to a maximum of 12 cycles. It is necessary to monitor at least the first cycle with ultrasonography because of the risk of multiple pregnancy and the variable response of patients to different doses of clomiphene. In addition, the risk of ovarian hyperstimulation syndrome should not be underestimated. More triplets and higher order pregnancies result from ovulation induction than from in vitro fertilization, and multiple pregnancy has many risks for both mother and babies. The role of empirical clomiphene in the treatment of unexplained infertility is debatable and the present data are inconclusive. Obesity, hyperandrogenaemia and insulin resistance are important factors in clomiphene-resistant patients. Failure to ovulate in response to clomiphene has been approached by either medical or surgical treatment. An effective alternative medical treatment is gonadotrophin injections. Treatment with metformin and the new generation of insulin-sensitizing drugs is under evaluation. The most widely used surgical treatment today is laparoscopic ovarian drilling, which appears to be as effective as gonadotrophin therapy.     

Evaluation of unilateral versus bilateral ovarian drilling in clomiphene citrate resistant cases of polycystic ovarian syndrome

Objectives  Laparoscopic ovarian drilling (LOD) has been put forward as the treatment of choice in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS), with tubo-ovarian adhesion formation as the major disadvantage. Our study proposed to compare the efficacy of laparoscopic unilateral ovarian drilling with bilateral ovarian drilling in terms of ovulation and pregnancy rate with the expected advantage of decreasing postoperative adhesion rate and change in fimbiro ovarian relationship with unilateral drilling. Methods  This prospective randomized study included 44 patients with anovulatory infertility due to PCOS. Twenty-two patients underwent unilateral ovarian drilling in group-I and 22 patients underwent bilateral ovarian drilling in group-II between June 2005 and June 2007. The number of drilling site in each ovary was limited to five. The clinical and biochemical response, ovulation and pregnancy rates over a follow-up period of 1 year were compared. Tubo-ovarian adhesion rate was compared during cesarean section or during repeat laparoscopy. Results  There was no statistical difference between the two groups in terms of clinical and biochemical response, ovulation rate and pregnancy rate. Postoperatively, tubo-ovarian adhesions could be assessed in 36.3% of the patients and no adhesions were found in a single case in either group. Conclusion  Unilateral drilling cauterization of ovary is equally efficacious as bilateral drilling in inducing ovulation and achieving pregnancy. Unilateral ovarian drilling may be a suitable option in clomiphene citrate resistant infertility patient of PCOS which can replace bilateral ovarian drilling with the potential advantage of decreasing the chances of adhesion formation.     

Surgical treatment of polycystic ovary syndrome associated with infertility

Laparoscopic ovarian drilling is a relatively simple procedure performed by minimal access and usually on an outpatient basis. It provides an alternative treatment option for polycystic ovary syndrome (PCOS) patients anovulatory to clomiphene citrate. The mechanism of action of laparoscopic ovarian drilling is unclear; its beneficial effect is apparently due to destruction of the androgen-producing stroma. The procedure appears to have little or no effect on insulin sensitivity and lipoprotein profile. The majority (56-94%) of PCOS patients who are clomiphene citrate resistant ovulate after drilling, and at least half of them go on to achieve a pregnancy. Predictive factors for pregnancy are younger age and lower body mass index. The endocrine changes resulting from ovarian drilling last for an extended period of time. Exogenous gonadotrophin treatment and laparoscopic ovarian drilling appear to yield comparable ovulation and pregnancy rates; however, multiple pregnancy is rare with drilling. There are several complications associated with the procedure, including post-operative periadnexal adhesion formation. Alternative treatment options, including lifestyle modification (diet and exercise) and metformin, may well reduce the need for ovarian drilling in well-selected cases. Progress in understanding of this complex syndrome and effective new treatments will further diminish the need for surgery.     

多囊卵巢综合征手术治疗的利与弊

多囊卵巢综合征是育龄期妇女最常见的一种内分泌紊乱性疾病,排卵障碍是该类患者不育的主要原因,常用解决方法为促排卵治疗。促排卵药物,例如氯米芬临床效果好,普遍采用。但是,部分患者耐药。手术治疗,特别是腹腔镜下卵巢打孔术是目前用于氯米芬耐药的多囊卵巢综合征患者促排卵治疗的二线治疗方案,本文就卵巢手术的主要方式、腹腔镜下卵巢打孔术的适应人群、术后效果及手术并发症进行简单概括。     

Strategies for the use of insulin-sensitizing drugs to treat infertility in women with polycystic ovary syndrome

OBJECTIVE: Insulin resistance and its compensatory hyperinsulinemia play a key pathogenic role in the infertility of the polycystic ovary syndrome. Numerous studies indicate that insulin-sensitizing drugs can be used to enhance spontaneous ovulation and the induction of ovulation in the syndrome. The aim of this review is to summarize the studies in which insulin-sensitizing drugs were used to increase ovulation rate or improve fertility in women with the PCOS and to translate the information into practical guidelines for the use of these drugs by reproductive endocrinologists. DESIGN: Review and critique of studies in which an insulin-sensitizing drug was used to increase ovulation rate or improve infertility in women with the polycystic ovary syndrome. MAIN OUTCOME MEASURE(S): Ovulation rate and pregnancy rate. RESULT(S): Studies have demonstrated that insulin-sensitizing drugs can increase spontaneous ovulation, enhance the induction of ovulation with clomiphene citrate, and increase clinical pregnancy rates. CONCLUSION(S): An algorithmic approach is provided for the use of insulin-sensitizing drugs to treat the anovulation and infertility of women with the polycystic ovary syndrome.