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FOR WOMEN WHO HAVE PCOS in Laparoscopic Ovarian Drilling, an Insulated Needle Unipolar Electrode Is Ma 36 return toFSHcyclicityin80%of cases. infollicle-stimulating hormone(FSH),and level,increase in testosterone forthe reduction isresponsible stroma destruction ofandrogen-producing butitisthoughtthatthe each point.Themechanismofaction isunclear, for2secondsat using40wattsofcoagulatingcurrent spaced punctures 6to12evenly inserted intheovaryperpendicular tothesurfacecreate is ovariandrilling,aninsulated needleunipolarelectrode In laparoscopic PCOS FOR WOMENWHOHAVE OBG Management | February 2011 | Vol. 23 No. 2 obgmanagement.com cHristy kraMeS for obg MaNaGeMent UPdAtE FERtILItY Two experts discuss the detrimental reproductive effects of obesity; the challenge of preventing ovarian hyperstimulation; and why 4 million or so “outcomes” validate Prof. robert edwards’s Nobel Prize in Physiology or Medicine ›› G. david Adamson, Md ›› Mary E. Abusief, Md Dr. Adamson is Director of Fertility Physicians Dr. Abusief is a Board-Certified Specialist in of Northern California in Palo Alto and San Jose; Reproductive Endocrinology and Infertility at Adjunct Clinical Professor at Stanford University Fertility Physicians of Northern California in Palo School of Medicine; Associate Clinical Professor at Alto and San Jose, Calif. the University of California, San Francisco, School of Medicine; and Past President of the American Society for Reproductive Medicine. The authors report no financial relationships relevant to this article. mpaired fertility is no small problem. • We know more about the effects of obe- I According to the Centers for Disease Con- sity on fecundity, and more about how to trol and Prevention (CDC), it affects 7.3 mil- increase the likelihood of pregnancy and lion women 15 to 44 years old in the United live birth in obese women • The development of in vitro fertilization In thIs States alone, or approximately 10% of the Article female population of reproductive age.1 (IVF) more than 30 years ago represents a Not long ago, there was little to be done significant achievement and vast benefit the grand about the problem. Today, however, we have to mankind, noted the Nobel Committee achievement of IVF many tools and tactics at our disposal, and in awarding the 2010 prize for Physiology page 40 another CDC statistic demonstrates their or Medicine to Robert Edwards, PhD efficacy: Fewer than one third of women • Ovarian hyperstimulation syndrome after who have received medical intervention for controlled ovarian stimulation cannot be Proposed grading impaired fertility in the past year continue to avoided completely—but its likelihood system for ovarian experience the problem.1 can be reduced significantly through care- hyperstimulation In this article, we highlight three recent ful assessment of the patient and a cau- syndrome developments in fertility: tious approach to ovarian stimulation. page 42 Hear dr. Adamson describe strategies Be mindful of the effects of obesity to avert ovarian hyperstimulation, on a woman’s reproductive function at obgmanagement.com bese patients are almost three times as ovulatory dysfunction. The hypothalamic- Olikely as women of normal weight to pituitary-ovarian (HPO) axis is also affected be infertile. Polycystic ovarian syndrome by overweight and obesity, resulting in (PCOS) is generally unmasked or exacer- oligo-ovulation in 30% to 47% of women.2 bated, or both, by obesity, and the hyperan- Some studies suggest that fecundity may be drogenicity associated with PCOS can cause reduced in ovulatory obese women as well obgmanagement.com Vol. 23 No. 2 | February 2011 | OBG Management 37 UPdAtE fertility as those with ovulatory dysfunction.2 Most pregnancy-associated complications. How- obese women are not infertile, however. ever, it is not always successful and can have Once pregnancy is achieved, the risk complications of its own. of miscarriage is elevated in obese women (odds ratio [OR] ~1.67), and the live birth rate is lower (OR ~0.75), compared with women What can you offer to of normal weight.2–4 Obese women also have obese patients who an elevated risk of miscarriage after egg experience infertility? donation (OR ~1.52) and ovulation induction • Clomiphene citrate is the most com- (OR ~5.11). There is no evidence that the rate monly used ovarian-stimulation agent of miscarriage is increased after IVF, com- for oligo-ovulation that arises from PCOS pared with other treatments. or HPO-axis disruption; it is most effec- The diagnosis of infertility is difficult in tive in patients of normal weight.4,6 The obese patients because the pelvic examina- protocols associated with clomiphene tion is less informative, although ultrasonog- administration in obese patients are sim- raphy (US) is usually helpful.5 In addition, ilar to those for women of normal weight; obesity can blur the distinction between so are results, although the pregnancy PCOS and HPO axis-related oligo-ovulation. rate is not as high in obese women. Laparoscopy and other diagnostic interven- • Gonadotropins are effective ovarian- tions are performed less frequently in obese stimulation drugs that are used in hypo- women, and complications of diagnostic thalamic hypogonadal patients as well as laparoscopy are higher in this population.3 after failed treatment with clomiphene citrate. Gonadotropins can be effective even in very obese patients; the dosage take the initiative in increases with body mass index (BMI).4,6 recommending weight loss • Metformin reduces insulin resistance in Even a reduction As health-care providers, we need to be more women who have PCOS. By itself, met- as small as 5% to proactive in recommending lifestyle changes formin is ineffective at inducing ovula- 10% of body weight for obese women so that they lose weight tion and has not proved to increase the can improve fertility before pregnancy. Women who have infertil- pregnancy rate when it is added to clo- ity are usually very motivated to conceive; as miphene.5 Nevertheless, it is commonly a result, they may also be motivated to lose given at a daily dosage of 1,000 to 2,000 weight. Caloric restriction, increased physi- mg to women who have hyperinsu- cal activity, behavioral modification, and linemia, and it may reduce the miscar- professional expertise are all essential for riage rate in women who have PCOS. successful weight loss.2 Even a reduction as • Other medications that have been used small as 5% to 10% of body weight can have to enhance ovulation in obese women clinical benefit.2,4,5 include dexamethasone to reduce ele- Metformin is an additional option. vated androgen levels, bromocryptine When combined with a low-calorie diet, for elevated prolactin levels, and thyroid metformin may lead to weight loss, restore hormone for hypothyroidism. ovulation, and improve fecundity in women • Among obese women who have oligo- who have PCOS.2 ovulation, ovarian drilling (FIGURE, Bariatric surgery is now commonly page 36) is generally reserved for patients reserved for women whose body weight is who have not responded to clomiphene 45 kg or more above normal. Bariatric sur- or gonadotropins. This procedure has gery can improve the altered hormone pro- proved to be as effective as clomiphene file, including elevated thyroid-stimulating administration, with the advantage hormone (TSH), of obese women. It also that it does not increase the risk of mul- appears to improve fecundity and reduce tiple gestation and leads to longstanding 38 OBG Management | February 2011 | Vol. 23 No. 2 obgmanagement.com UPdAtE fertility improvement in one third of patients.5 ovarian reserve. Ovarian drilling is a modification of ovar- • Assisted reproductive technology ian wedge resection for women who have (ART) is sometimes used in this popu- PCOS. The mechanism of action is not lation, but it is less likely to lead to clear, but it is thought that destruction pregnancy and live birth, for unknown of adrogen-producing stroma causes an reasons.2,3 We inform obese women that immediate reduction in testosterone, an a BMI below 30 is desirable before ART. increase in follicle-stimulating hormone (FSH), and a return to FSH cyclicity in WHAt tHIS EVIdENCE MEANS 80% of cases. These effects can persist FOR PRACtICE for several years, and a pregnancy rate of approximately 60% can be attained in Overall, the management of infertility in less than 6 months. Clomiphene-resis- obese women is extremely challenging tant women may be more responsive to because of its multiple causes—many the drug after ovarian drilling, and the of which are still not well understood. However, the profound implications of risk of ovarian hyperstimulation appears obesity for all aspects of reproduction to be reduced. Ovarian drilling is less make it imperative that we pay more effective in obese women than in women attention to identification and treatment of normal weight. Complications include of obesity in the infertile population. adhesions around the ovary and reduced IVF is cited by Nobel Committee for its “benefit to mankind” n December 10, 2010, Robert Edwards, Physiology or Medicine for his innovative and OPhD, was awarded the Nobel Prize in pioneering work to create IVF. In presenting the award, the Committee noted that Profes- sor Edwards’ work “represents a monumen- tal medical advance that can truly be said to confer the greatest benefit to mankind.” Professor Edwards is the embryologist who performed the basic science and labo- ratory work, along with Dr. Patrick Steptoe, who provided clinical care, which led to the birth of the world’s first IVF baby, Lou- ise Brown, on July 25, 1978. Since then, IVF has become the most successful treatment for infertility and is available in more than 100 countries. The delivery rate for each single IVF attempt is about 25% globally; it more than doubles in selected patients S e G who have a good prognosis. In some coun- a im tries, almost 5% of all births arise from IVF; y in the United States, that figure is about 1%. tt : Ge Prof. robert edwards (left) holds the infant Louise Brown The International Committee Monitoring hoto ART (ICMART) estimates that more than P 40 OBG Management | February 2011 | Vol.
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