Clinical Review

2011 Update on fertility

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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


 

References

Impaired fertility is no small problem. According to the Centers for Disease Control and Prevention (CDC), it affects 7.3 million women 15 to 44 years old in the United States alone, or approximately 10% of the female population of reproductive age.1

Not long ago, there was little to be done about the problem. Today, however, we have many tools and tactics at our disposal, and another CDC statistic demonstrates their efficacy: Fewer than one third of women who have received medical intervention for impaired fertility in the past year continue to experience the problem.1

In this article, we highlight three recent developments in fertility:

  • We know more about the effects of obesity on fecundity, and more about how to increase the likelihood of pregnancy and live birth in obese women
  • The development of in vitro fertilization (IVF) more than 30 years ago represents a significant achievement and vast benefit to mankind, noted the Nobel Committee in awarding the 2010 prize for Physiology or Medicine to Robert Edwards, PhD
  • Ovarian hyperstimulation syndrome after controlled ovarian stimulation cannot be avoided completely—but its likelihood can be reduced significantly through careful assessment of the patient and a cautious approach to ovarian stimulation.

Be mindful of the effects of obesity
on a woman’s reproductive function

Obese patients are almost three times as likely as women of normal weight to be infertile. Polycystic ovarian syndrome (PCOS) is generally unmasked or exacerbated, or both, by obesity, and the hyperandrogenicity associated with PCOS can cause ovulatory dysfunction. The hypothalamic-pituitary-ovarian (HPO) axis is also affected by overweight and obesity, resulting in oligo-ovulation in 30% to 47% of women.2 Some studies suggest that fecundity may be reduced in ovulatory obese women as well as those with ovulatory dysfunction.2 Most obese women are not infertile, however.

Once pregnancy is achieved, the risk 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 of normal weight.2–4 Obese women also have an elevated risk of miscarriage after egg donation (OR ~1.52) and ovulation induction (OR ~5.11). There is no evidence that the rate of miscarriage is increased after IVF, compared with other treatments.

The diagnosis of infertility is difficult in obese patients because the pelvic examination is less informative, although ultrasonography (US) is usually helpful.5 In addition, obesity can blur the distinction between PCOS and HPO axis-related oligo-ovulation. Laparoscopy and other diagnostic interventions are performed less frequently in obese women, and complications of diagnostic laparoscopy are higher in this population.3

Take the initiative in recommending weight loss

As health-care providers, we need to be more proactive in recommending lifestyle changes for obese women so that they lose weight before pregnancy. Women who have infertility are usually very motivated to conceive; as a result, they may also be motivated to lose weight. Caloric restriction, increased physical activity, behavioral modification, and professional expertise are all essential for successful weight loss.2 Even a reduction as small as 5% to 10% of body weight can have clinical benefit.2,4,5

Metformin is an additional option. When combined with a low-calorie diet, metformin may lead to weight loss, restore ovulation, and improve fecundity in women who have PCOS.2

Bariatric surgery is now commonly reserved for women whose body weight is 45 kg or more above normal. Bariatric surgery can improve the altered hormone profile, including elevated thyroid-stimulating hormone (TSH), of obese women. It also appears to improve fecundity and reduce pregnancy-associated complications. However, it is not always successful and can have complications of its own.

What can you offer to obese patients who experience infertility?

  • Clomiphene citrate is the most commonly used ovarian-stimulation agent for oligo-ovulation that arises from PCOS or HPO-axis disruption; it is most effective in patients of normal weight.4,6 The protocols associated with clomiphene administration in obese patients are similar to those for women of normal weight; so are results, although the pregnancy rate is not as high in obese women.
  • Gonadotropins are effective ovarian-stimulation drugs that are used in hypothalamic hypogonadal patients as well as after failed treatment with clomiphene citrate. Gonadotropins can be effective even in very obese patients; the dosage increases with body mass index (BMI).4,6
  • Metformin reduces insulin resistance in women who have PCOS. By itself, metformin is ineffective at inducing ovulation and has not proved to increase the pregnancy rate when it is added to clomiphene.5 Nevertheless, it is commonly given at a daily dosage of 1,000 to 2,000 mg to women who have hyperinsulinemia, and it may reduce the miscarriage rate in women who have PCOS.
  • Other medications that have been used to enhance ovulation in obese women include dexamethasone to reduce elevated androgen levels, bromocryptine for elevated prolactin levels, and thyroid hormone for hypothyroidism.


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