Obesity’s impact on adverse reproductive sequelae and altered hormonal milieu has been described [12–15] and different mechanisms have been proposed as discussed elsewhere in this book. In general, obesity increases the risk of anovulation and menstrual cycle abnormalities. In ovulatory women menstrual cycle length is altered with obesity manifesting as a longer follicular phase and a shorter luteal phase. Associated mechanisms are discussed elsewhere in this book, but briefly, it has been demonstrated that as BMI increases, follicular phase is lengthened and the luteal phase is shorter [12]. These changes are associated with decreased urinary luteinizing hormone (LH) and follicle stimulating hormone in the follicular phase, and decreased luteal phase pregnanediol-3-glucuronide (Pdg), a progesterone metabolite. Overall this suggests corpus luteum dysfunction with decreased capacity for implantation and maintenance of a healthy pregnancy. Consistent with this, a separate study also demonstrated reduced LH pulse amplitude and lower levels of urinary Pdg in ovulatory morbidly obese women, again indicating altered function of the corpus luteum [13].

Adipokines are hormones produced by adipose tissue, and a number of adipokines have been implicated as having effects on reproductive physiology including adiponectin, resistin, and leptin. Of these leptin is perhaps the best studied. Leptin secretion correlates directly with total body adiposity. Obese women have excess serum leptin concentrations with subsequent inhibition of ovarian steroidogenesis and follicular growth [16]. A study examining the contrary scenario, found that leptin administration in women with hypothalamic amenorrhea due to strenuous activity or low weight resulted in a resumption of gonadotropin secretion, follicular development, and ovulation, demonstrating the important physiologic role that leptin plays in female reproductive function [17].

Polycystic Ovarian Syndrome (PCOS) is associated with obesity, anovulation, and insulin resistance and other metabolic derangements. About 30–70 % of patients with PCOS are obese [18]. Insulin resistance and a hyperinsulinemic state in PCOS patients lead to stimulation of excess androgen production that inhibits normal follicular growth and maturation [19]. This then leads to oligo- and anovulation in many women with PCOS, with subsequent subfertility. The ovulatory dysfunction associated with PCOS has been attributed primarily to the hyperandrogenic environment, but is augmented by factors associated with obesity, i.e., hyperinsulinemia and increased levels of leptin [14, 15].

Bariatric surgery restricts caloric intake and nutrient absorption, thereby promoting weight loss and decreasing overall total body adiposity. Leptin concentrations decrease with weight loss after bariatric surgery and research in murine models have shown improved fertility after reduction of leptin levels after decreased caloric intake and dietary modification [20, 21]. A recent study investigating leptin levels after bariatric surgery demonstrated that, regardless of the type of surgical procedure, levels of leptin and insulin resistance significantly decreased following bariatric surgery, further suggesting that weight loss alters the endocrinologic balance [22]. Also, cytokines such as interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1) are higher in obese women and can contribute to ovulatory dysfunction and implantation failure. Levels of these cytokines are lower after bariatric surgery, which help improve ovulatory function and implantation [23].

A 2006 survey of 98 anovulatory women found that 70 of these women regained ovulatory function after bariatric surgery, and that average weight loss was higher among those who regained ovulatory function compared to those who did not (61.4 vs. 49.9 kg respectively) [24]. This is consistent with a 1998 survey of 56 anovulatory overweight women showing that 90 % of women regained ovulatory menstrual cycles after bariatric surgery. In this study, women who regained ovulatory function also had an overall greater average weight loss compared to women who did not regain function [25]. In a recent study of 20 obese women with PCOS who underwent LRYGB, with a mean follow-up time of nearly 4 years, 82 % experienced normalization of their menstrual cycles and of those patients who had not conceived prior to surgery (50 %), all patients who further desired pregnancy became pregnant within 3 years [26]. In another study of 24 obese women with PCOS who underwent LRYGB, all women resumed normal menstrual cycles after a mean of 3.4 months postoperatively. Eighteen of 23 subjects had moderate to complete resolution of hirsutism. The study also notes that of the five subjects who were infertile prior to surgery, all women were able to conceive without ovulation induction using clomiphene postoperatively [27]. However, given that most of these studies are retrospective with small sample sizes, the current lack of well-designed studies does not allow for definite conclusions or formal recommendations to be made regarding the reproductive benefit of bariatric surgery in women with PCOS.

In regards to ovulatory women undergoing bariatric surgery, a recent study by Legro et al. demonstrated improved, shorter follicular phase length from 22 days preoperatively to approximately 14 days after bariatric surgery [28]. The study also noted improved hyperandrogenemia and sexual function after bariatric surgery. In a follow-up study, investigators measured urinary excretion of LH and Pdg during the luteal phase before and after bariatric surgery in obese women. Levels of both hormones increased post-surgery, but still remained below levels seen in controls [28]. Taken together these data suggest that while bariatric surgery may help improve ovulatory function in obese women, there may be a certain amount of weight loss required to completely restore function, or perhaps there are lingering effects of obesity on the hypothalamic–pituitary–ovarian axis after weight loss surgery.

Based on available literature, it is difficult to conclude whether bariatric surgery improves fertility per se, as most studies that have reported on fertility following bariatric surgery demonstrate that not all patients prior to surgery struggled with infertility or even attempted pregnancy. On the other hand, it is well established that weight loss with bariatric surgery improves ovulatory function and menstrual regularity as discussed above.

In a 2008 systematic review by Maggard et al., authors identified a number of studies demonstrating improved menstrual regularity, ovulation, and improvements in androgen levels after bariatric surgery, but only six studies specifically addressing female fertility after bariatric surgery [6]. One of the identified studies compared preoperative and postoperative reproductive histories of women who underwent bariatric surgery and had lost greater than 50 % of excess weight. 29/115 women (25 %) had reported infertility prior to bariatric surgery and there was data on nine women who conceived after surgery. Of these women 8 were in the group that had reported infertility prior to surgery. While this data is helpful, it is difficult to deduce any causal effects given that the follow-up time was not mentioned in this study and the number of patients who tried to conceive prior to surgery was unknown. The difficulty of determining how many patients actually desired pregnancy preoperatively or postoperatively is a common theme seen in studies.

In regards to fertility after specific types of bariatric procedures, there is one recent study. This study conducted in Italy and published in 2012, investigated 110 women who had undergone bariatric surgery (intragastric balloon placement, LAGB, sleeve gastrectomy, and LRYGB) who were identified with subfertility prior to surgery [29]. After surgery, 69 % of those patients became pregnant, with greater weight loss and lower BMI being positively associated with pregnancy. The endocrinologic changes that take place with significant weight loss were not investigated in the study. The authors did not find a difference in pregnancy rates across the different types of bariatric surgical methods.

Although the data looking specifically at female fertility is limited, since the main premise of bariatric surgery is weight loss and any improvement of fertility may be an “unintended” outcome, at minimum, physicians can counsel patients by stating that research indicates that surgical intervention via bariatric surgery may have a benefit on future fertility. One can infer that although there is limited evidence of improved fertility as gauged by increased pregnancy rates, there is ample evidence that hormone levels and menstrual cycles do seem to normalize in women post-surgery via the multiple physiologic mechanisms previously described in this chapter.

Despite the fact that bariatric surgery may improve ovulatory function and fertility in obese women, some women who undergo bariatric surgery may still require aggressive fertility treatment like in vitro fertilization (IVF). Despite this, few data exist regarding IVF in women who have undergone bariatric surgery. In a case series by Doblado et al., the authors show evidence that IVF is safe and effective in women who have undergone bariatric procedures [30]. On the other hand, the authors raise the point that special considerations need to be made for women who have undergone bariatric surgery in the setting of IVF. First, the authors state that ovarian hyperstimulation syndrome could lead to serious complications including ascites and increased intraabdominal pressure which could in turn increase the risk of intestinal obstruction and internal hernia, two late complications of bariatric surgery. Internal hernia presents clinically with nausea and abdominal pain which could mimic OHSS.

Overall, there seems to be sufficient evidence to suggest that obesity adversely impacts IVF outcomes, however, it is difficult to deduce based on existing literature if weight loss actually improves clinical pregnancy rate and live birth outcome in women undergoing IVF. Given that little has been published on the impact of surgical intervention on IVF outcomes, it would be difficult to counsel patients that undergoing bariatric surgery prior to undergoing IVF would be beneficial. Furthermore, patients and physicians must weigh the risks and benefits of surgical weight loss and the delay in time to conceive that one must account for following surgery. More work is needed to investigate the true impact of weight loss via surgical intervention on the outcome of IVF.

The optimal timing of conception after bariatric surgery has not been determined, as the trajectory of weight loss and recovery for each patient is different. However, rapid weight loss generally plateaus after 18 months post-surgery, after which, the concerns for nutritional deficiencies are somewhat diminished. Constrained by the limited nature of research on this topic, the American College of Obstetricians and Gynecologists (ACOG) published a practice bulletin in 2009 that does not make any recommendations regarding the timing of conception, but ACOG recommends closer surveillance of maternal weight and nutritional status, in addition to regular ultrasounds for serial monitoring of fetal growth, for those women who conceive <12 to 24 months after bariatric surgery [31].