Open access peer-reviewed chapter

Reproductive Consequences of Obesity

Written By

Tamara Hunter and Roger Hart

Submitted: May 22nd, 2018 Reviewed: August 13th, 2018 Published: December 31st, 2018

DOI: 10.5772/intechopen.80897

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Abstract

With increasing global obesity, there is a growing body of research looking at the impact of this on reproduction. Both male and female fertility are impacted on by being overweight or obese. Although the pathophysiology is not clear, it appears that obesity impacts endocrine function in men and women, oocyte and sperm quality, embryo quality, endocrine receptivity, and implantation. Miscarriage, pregnancy, and live birth rates and the risk of congenital malformations are all influenced by obesity. Transgenerational health is also affected, with metabolic, endocrine, and reproductive outcomes in the offspring being negatively affected by both paternal and maternal obesity. It appears that weight loss results in improvements in these outcomes and various strategies have been employed including lifestyle and behavior modification, pharmacological agents, and also bariatric surgery. This chapter aims to explore the reproductive outcomes of obesity and how this can be best managed to improve outcomes.

Keywords

  • obesity
  • IVF
  • embryos
  • bariatric
  • fertility
  • offspring
  • reproduction
  • lifestyle
  • oocyte
  • sperm

1. Introduction

Overweight or obesity is defined as an accumulation of excess body fat that poses a risk for health [1]. A measure often used in assessment of this is the body mass index (BMI), which is a person’s weight in kilograms divided by height in meters squared (kg/m2). Obesity is a BMI greater than 30 and overweight is a BMI greater than 25, although in South East Asian populations, it is generally accepted that the upper limit of normal is a BMI of 23.

Globally, 39% of adults over 18 years are overweight and 13% are obese, and worldwide, obesity has tripled since the 1970s [2]. Being overweight or obese is directly linked to a greater risk of mortality and disease than being underweight.

Infertility is defined as failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse [3]. Globally, at least 50 million couples worldwide experience infertility, with the burden affecting up to one in four couples in developing nations. The overall prevalence of infertility does not appear to have changed since the 1990s.

Overweight or obesity is understood to impact on both female and male reproductive health, and mounting research demonstrates that this impact will extend to the health and reproductive outcomes of future generations.

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2. Effects of obesity on female reproduction

2.1 Hormonal effects of obesity

Menstrual irregularities occur more frequently in women who are overweight. This is due to a functional alteration to the hypothalamic-pituitary-ovarian (HPO) axis from various factors. Firstly, obesity induces a hyperinsulinemic state, separate to polycystic ovarian syndrome (PCOS). Hyperinsulinemia leads to a suppression in serum hormone binding globulin (SHBG), which results in an increase in bioactive androgens. These androgens are subsequently aromatized within body fat to estrogen, which suppresses gonadotrophins produced by the pituitary [4].

Elevated androgens in PCOS also lead to an increased deposition of visceral fat, exacerbating insulin resistance and hyperinsulinemia, further stimulating androgen production and perpetuating the cycle of pituitary suppression [5].

Additionally, adipokines, cytokines produced from adipose tissue, are known to impact on ovulation. Obese women have higher levels of circulating leptin, a cell-signaling protein from adipose tissue, than normal weight women, and this can therefore mean a chronic downregulation of the receptor in the hypothalamus, [6] resulting in suppression of the HPO axis activity. A study of eumenorrheic obese women demonstrated that the amplitude of luteinizing hormone (LH) pulses was significantly reduced compared with normal weight women, again pointing to a central defect [7].

Obese women remain subfertile even if they are ovulatory. Two studies in large cohorts of Danish women showed a decline in fecundability ratios with increasing BMI [8, 9]. Another large American cohort [10] along with a Dutch cohort of over 3000 women [11] also demonstrated a linear decline in spontaneous conception rates with rising BMI.

Consequently, there are other factors at play that affect fertility in overweight and obese women.

2.2 Effects of obesity on oocyte quality

Data show that being overweight or obese can have profound impact on oocyte quality. A study of over 45,000 assisted reproduction transfers demonstrated that a higher BMI resulted in a lower likelihood of successful pregnancy when autologous oocytes were used but not when oocytes from lean donors were used [12]. This has been demonstrated in other research as well [13].

Studies also suggest that obese women in in vitro fertilization (IVF) cycles require higher levels of gonadotrophin stimulation and longer treatment to achieve an oocyte retrieval [14]. This is also the case in superovulation for intrauterine insemination cycles [15]. Obese women also have a greater risk of cycle cancelation, lesser oocytes collected, and lesser oocyte maturity than normal weight women [16, 17, 18].

Several mechanisms are believed to impact on the oocyte quality in obese women.

Obesity is an inflammatory state where women have higher circulating levels of C-reactive protein (CRP), which is an inflammatory biomarker. Adipose tissue produces many proinflammatory adipokines including leptin, tumor necrosis factor alpha (TNFα), and interleukin (IL) 6. The reproductive tissues, like all tissues, are negatively affected by inflammation. The follicular environment is altered in an obese woman. Follicular fluid contains higher levels of insulin, triglycerides, leptin, and markers of inflammation such as lactate and CRP [6]. Leptin affects steroidogenic pathways in granulosa cells, thus affecting estrogen and progesterone production. This could therefore have impact downstream on endometrial receptivity and implantation [6].

In obese mouse models, the ovaries demonstrate more apoptotic follicles and the oocytes themselves are smaller and less likely to be mature. These oocytes reveal high rates of meiotic aneuploidy due to fragmented and disorganized meiotic spindles and chromosomes that are not properly aligned on the metaphase plate [6].

Independent from this, obesity alters mitochondrial function in the oocyte. In an obese mouse model, the mitochondria have a disordered architecture with fewer cristae, more vacuoles, and evidence of swelling [19]. These abnormal mitochondria show evidence of metabolic stress, which leads to a compensatory increase in mitochondrial DNA copy number in obese mice [6, 20]. Obese mice also demonstrate evidence of endoplasmic reticulum (ER) stress where their cumulous-oocyte complexes have increased ER stress markers and increased granulosa cell apoptosis [21].

A possible cause for this cellular and organelle damage in obesity is lipotoxicity. Lipotoxicity is a condition where fatty acids from the diet that exceed the storage ability of the adipocytes can accumulate in other tissues and cause toxic effects.

Obese women have higher circulating free fatty acids (FFAs), which increase reactive oxygen species (ROS) that induce mitochondrial and ER stress and leads to apoptosis. Studies have shown that the oocytes of mice have significant increased production of ROS along with depleted glutathione levels, which is an important intracellular antioxidant defense against ROS [22]. Oocytes exposed to maternal obesity or to high levels of FFA in vitro have demonstrated perturbed mitochondria with reduced mitochondrial function, which then fail to support normal cleavage and embryo development [21].

2.3 Effects of obesity on embryo quality

The preimplantation embryo is also affected by an obese environment. Given that the early embryonic development is largely driven by the oocyte, it is not unexpected that if the oocyte is negatively affected, then the embryo development would be too.

In a mouse model, embryos of obese females have demonstrated slower preimplantation development and disordered differentiation to inner cell mass and trophectoderm lineage [20].

In an IVF model with autologous oocytes, obese women are more likely to create poor quality embryos [23, 24]. One study noted that embryos from women with a BMI > 25 kg/m2 were less likely to develop after fertilization and those that did reached the morula stage more rapidly. Those that reached the blastocyst stage had fewer cells in the trophectoderm and demonstrated poor glucose uptake and increased levels of triglycerides along with altered amino acid metabolism compared with embryos from normal weight women (BMI < 25 kg/m2) [25].

Much like oocytes, embryos may also be susceptible to lipotoxicity. Murine embryos that are cultured in palmitic acid, the most common FFA present in human serum, have fewer nuclei and altered IGF-1 receptor expression [26]. This negatively affects insulin sensitivity and glucose transport at a critical stage in development. This study also demonstrated that the trophoblastic cells that are exposed to the palmitic acid proliferate less and undergo apoptosis in a dose-dependent fashion.

Elevated leptin levels also have a direct negative effect on the developing embryo. In vitro studies have demonstrated that leptin has a stimulating effect on human trophoblastic cell growth and inhibition of leptin decreases that proliferation and induces apoptosis [27]. Much like its effect in the brain, tonically elevated leptin levels in an obese state may decrease the sensitivity of trophoblastic cells to its effect, altering their development.

However, there are studies in human models that have not demonstrated a negative effect of obesity on embryo quality, showing no significant difference in the quality of transferred embryos between the different BMI groups [28, 29, 30, 31]. Although it is worth noting that despite the quality of transferred embryos being similar, other studies have suggested a reduction in the overall quality of all embryos created in an IVF cycle [14, 24], with fewer surplus embryos cryopreserved in an obese population compared to women with a normal BMI [14]. A retrospective analysis of IVF/ICSI cycles observed that in young women, obesity led to a significant reduction in average embryo quality, cryopreservation, and also embryo utilization [24]. A large retrospective analysis of over 6500 IVF cycles demonstrated no difference in embryo quality but did comment that there were poorer outcomes in the obese women [31]. Certainly, large prospective trials are required to further elucidate the effect of obesity on the embryo.

2.4 Effects of obesity on endometrial receptivity and implantation

There are conflicting data as to whether or not obesity affects endometrial receptivity and implantation of embryos, and there are several suggested mechanisms.

Leukemia inhibitory factor (LIF) has been implicated in the regulation of implantation, and a significant negative correlation between endometrial glandular LIF and BMI has been observed [32]. It has also been suggested that a state of relative hyperestrogenemia that is seen in obese women (due to aromatization of androgens to estrogen in adipose tissue) may also have a detrimental effect on receptivity [32].

Obesity is associated with insulin resistance and hyperinsulinemia. Elevated insulin levels have been associated with a reduction on glycodelin and insulin-like growth factor binding protein 1 (IGFBP1). Low levels of glycodelin have been associated with recurrent pregnancy loss, and IGFBP1 is an integral molecule involved in adhesion during implantation [32]. Derangement in these molecules may contribute to reduced receptivity in obese women.

As noted previously, obesity is an inflammatory state and obese women have been observed to have elevations in proinflammatory cytokines (IL6, TNFα), and these inflammatory markers are thought to exert negative effects on implantation [14].

Obese women also have a different pattern of endometrial gene expression during implantation than lean women [33], which is more pronounced when examined in the context of infertility. It is postulated that this is due to all or some of the abovementioned factors and the change in the intrauterine milieu of the obese women.

Although there are several plausible mechanisms as to how obesity impacts negatively on endometrial receptivity and implantation, the data for impact on infertility are inconsistent and contradictory. The best model for discriminating between the obesity effects on oocyte/embryo and endometrium is the oocyte donation model [34]. A retrospective review of over 2500 oocyte donation cycles demonstrated a negative trend in pregnancy rates with a rising BMI and a statistically significantly lower pregnancy rate in overweight and obese women compared to normal weight women [35]. However, the implantation rates were considered similar, suggesting the difference between groups was due to an increased pregnancy loss rate in the obese women. Another study also demonstrated lower live birth rates among obese surrogates compared to normal weight women [36]. Other smaller studies have suggested no difference in outcomes in obese oocyte recipients [37].

A case-controlled trial looking at IVF with autologous oocytes observed that women with a BMI > 25 kg/m2 had reduced implantation and pregnancy rates along with increased miscarriage rates [38]. Once again, large well-designed prospective studies using this model are required to further examine the effect of obesity on endometrial receptivity and implantation.

2.5 Effects of obesity on miscarriage

The role of obesity and miscarriage is also debated. Given the recognized impact of obesity on both the embryo and the endometrium, it is a reasonable assumption that miscarriage rates would be higher in an overweight and obese population.

Several studies have demonstrated ever-increasing odds of miscarriage with increasing BMI, in ovulation induction for anovulatory infertility, as well as in IVF cycles in both fresh and frozen cycles [28, 17, 39, 40]. A large meta-analysis of over 47,000 cycles confirmed that overweight or obese women have a higher rate of miscarriage compared with normal weight women [41]. This has also been demonstrated in donor oocyte cycles, with higher miscarriage rates in obese recipients than in normal weight women [42].

Interestingly, however, a larger follow-up study of over 2600 donor oocyte cycles by the same group [43] did not demonstrate a difference in miscarriage rates. There was a trend toward a negative impact; however, it was only when a composite measure of ongoing pregnancy rate per cycle was calculated that this was shown to be significantly lower in the obese population.

A meta-analysis looking at both spontaneous and assisted reproduction pregnancies showed that women with a BMI > 25 kg/m2 had a significantly higher rate of miscarriage <20 weeks gestation. Subgroup analysis confirmed this to be in the donor oocyte cycles but not across all patients in the studies [44]. Another study demonstrated that in a group of women with a history of recurrent pregnancy loss (RPL), obesity is a well-recognized risk factor for miscarriage in a subsequent pregnancy [45].

A striking study looking at the chromosomal make-up of miscarried specimens from patients with RPL demonstrated that obese women had a much higher rate of euploid pregnancy loss compared to normal weight women. This supports the theory of the impact of obesity on embryo quality and endometrial receptivity.

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3. Effects of obesity on male reproduction

Historically, the impact of obesity on reproduction has largely been researched in female populations with very little examination of the impact of male obesity. There is, however, a growing body of research to indicate that obesity in the male is a cause for concern. A systematic review of 30 studies with over 115,000 participants found that obese men were more likely to experience infertility and that clinical pregnancy and live birth rates per assisted reproduction cycle were reduced.

3.1 Hormonal effects of male obesity

Much like in the female, the hypothalamic-pituitary-gonadal (HPG) axis is dysregulated in the setting of male obesity. There is strong evidence of a negative effect of obesity on total testosterone, SHBG, and free testosterone [46] as well as reduced inhibin B concentrations and diminished luteinizing hormone (LH) pulse amplitude [4]. It is well understood that suppression of SHBG by hyperinsulinemia in obese men increases androgen availability for aromatization to estrogen in adipose tissue, which may then lead to negative feedback and reduction in gonadotrophin secretion [4]. Consequent to this is a decreased Leydig cell testosterone secretion, which ultimately affects spermatogenesis.

The function of the Sertoli cell, which provides both physical and nutritional support to the developing germ cell, is also impacted. Adhesion of the Sertoli cell is dependent on testosterone, and a reduction in these levels can lead to retention and phagocytosis of mature spermatids and ultimately reduced sperm counts. Other hormones that influence Sertoli cell function, FSH, LH, inhibin B, and SHBG are all lower in obese men [47].

3.2 Effects of obesity on spermatogenesis

The best markers to assess the impact of obesity on spermatogenesis are the sperm parameters from the semen analysis (count, motility, and morphology). Rodent models clearly demonstrate that diet-induced male obesity leads to reduced sperm motility, decreased sperm count, and decreased percentage of sperm with normal morphology [47], though some argue that this is indirectly due to altered hormonal stimulation.

The impact of male obesity on sperm parameters in humans is more controversial, with many contradicting studies. A review of studies [47] demonstrated varying results for the impact of male obesity on sperm concentration, morphology, and motility. The reviewers commented that there were several significant confounders including lifestyle factors such as smoking and alcohol consumption as well as cofactors such as the metabolic syndrome, which have all been shown to impact on sperm parameters. Most of the cohorts studied come from fertility centers and so are biased toward subfertile men, who may differ from the background population. Additionally, many studies rely on self-reporting, which can lead to inaccuracies.

A recent systematic review that evaluated 21 studies demonstrated a J-shaped correlation between male obesity and sperm count, whereby overweight and obesity is associated with higher rates of oligozoospermia and azoospermia [48].

3.3 Effects of obesity on sperm DNA integrity

In addition to sperm parameters, sperm DNA integrity has been found to be an important factor for the ability of a sperm to generate a healthy pregnancy [49]. Reactive oxygen species (ROS), commonly elevated in subfertile men, have been found to impair sperm DNA integrity. This is likely due to the fact that sperm are highly susceptible to ROS in the later stages of spermiogenesis as they lose the majority of their antioxidant defenses when they shed cytoplasm (Figure 1).

Figure 1.

Hypothesis on how epigenetic changes and impact of ROS due to an obese proinflammatory environment can occur at multiple different points along the development of the sperm, resulting in altered fertility [47].

Studies have demonstrated that there is a positive correlation between increasing adiposity and higher sperm and seminal plasma ROS levels [50, 51, 52]. Oxidative stress is highly correlated with cumulative damage in the body induced by free radicals that are inadequately neutralized by antioxidant mechanisms. Antioxidant enzymes include superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST). A recent study in an obese mouse model showed decreased SOD in the testicular tissues of obese rats [53].

Studies have also confirmed that male obesity is associated with higher levels of sperm DNA damage [47], due to the oxygen-free radical damage, and a direct thermal effect on the testicles due to obesity. It is therefore a reasonable assumption that male obesity negatively impacts on sperm DNA integrity via high ROS levels within the testis. DNA fragmentation has been proven to reduce male fertility, possibly reduce success with assisted reproduction, and increase pregnancy loss.

Although not directly impacting on testicular function, obesity leading to reduced testosterone results in a reduction in libido and negatively impacts on erectile and ejaculatory function, which all lead to a reduction in fecundity [54].

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4. Transgenerational effects of parental obesity

There is good evidence to show that maternal obesity during pregnancy is a risk factor for obesity in the offspring [55]. There is also an increasing body of evidence that obesity in males and females periconceptionally can impact on the metabolic health and even fertility of future generations. By using animal models, the impact of maternal and paternal obesity on offspring and future generations has been examined. Studies have demonstrated that obesity and other health conditions can be transmitted across multiple generations via epigenetic mechanisms down either the maternal or the paternal line.

An elegant murine study by Huypens and others [56] induced obesity in both male and female parents for 6 weeks with a high-fat diet (HFD) and then performed IVF. Embryos created from all combinations of parents were transferred into a lean dam, to negate the impact of obesity during pregnancy (Figure 2).

Figure 2.

Embryos created from different combinations of obese and lean parents were transferred into a lean surrogate dam, to determine the impact of overweight and obesity in male and female parents on the next generation [55].

Female offspring born from both maternal and paternal obese parents gained more weight than the male offspring. The risk of female offspring obesity was reduced if only the female parent was obese, suggesting an additive effect.

Females from obese parents also had significant metabolic derangements. They demonstrated a delay in blood glucose clearance leading to hyperinsulinemia and increased fat mass. Male offspring demonstrated severe insulin resistance before any change in body weight. This insulin resistance was acquired in the offspring via the maternal line.

Another study by Fullston and others [57] demonstrated that paternal obesity initiated changes to metabolic health and obesity in multiple subsequent generations. Insulin resistance and obesity were transmitted to both the female and male first-generation offspring and then through both parental lineages to the second generation with amplified obesity in the female offspring in the first generation and in their sons in the second generation.

Epigenetics is the hypothesized mechanism for transgenerational disease patterns. It was thought that this was in utero exposure to epigenetic modification of offspring DNA or histone modification during developmental stages without alteration to the DNA itself. However, this has been broadened to include transgenerational (meiotic) alterations and occurs through several possible processes including DNA methylation, histone modification, DNA-binding proteins, and noncoding RNA [6] (Figure 1).

In the study by Fullston and others [57], they demonstrated that diet-induced paternal obesity leads to an alteration in mRNAs and microRNAs within the rodent testes, with alteration in the sperm microRNA content as well. They also detected 25% reduction in global methylation of germ cell DNA. These modifications are potential signals to program obesity and impaired metabolic health in offspring. These effects have also been demonstrated in humans with hypomethylation of sperm being associated with subfertility [58]. Another study [59] demonstrated, in a mouse model of diet-induced obesity, sperm tRNA-derived small RNAs impaired offspring glucose tolerance and induced insulin resistance. Other studies have also demonstrated that both maternal and paternal obesity can cause epigenetic changes that predispose offspring to obesity or metabolic disease later in life [60].

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5. Effectiveness of weight loss strategies

There is no doubt that obesity contributes to significant periconceptional and perinatal morbidity and has been clearly associated with prolonged time to conception, increased pregnancy loss, and higher rates of adverse pregnancy outcomes such as preeclampsia and gestational diabetes along with preterm birth and in turn increased fetal morbidity and mortality. As mentioned previously, there is increasing information that it affects fertility and miscarriage rates so it is not unexpected that national and international guidelines focus on weight loss prior to either spontaneous conception or assisted reproduction [4, 32, 61] and that first-line management is ideally with lifestyle intervention and behavior modification.

5.1 Lifestyle intervention and behavior modification

It is controversial as to whether weight loss through dietary intervention, exercise programs, or behavior modification will impact significantly on spontaneous conception rates or success with assisted reproduction. There are a group of studies that suggest improved ovulatory frequency, pregnancy rates, and cost per pregnancy achieved in assisted reproduction [32, 62]. One randomized controlled trial demonstrated that a 12-week diet and exercise program resulted in a mean weight loss of 5.4 kg in the intervention group, a trend toward a higher clinical pregnancy rate and a significant difference in live birth rates [63]. A secondary analysis of two parallel randomized controlled trials in obese PCOS women also demonstrated that deferred ovulation induction treatment preceded by lifestyle modification resulted in significantly improved ovulation rates and live birth rates when compared with immediate treatment [62]. Weight reduction in an obese anovulatory population has been shown to improve pregnancy rates. A 6-month lifestyle intervention induced an average weight loss of 10 kg, which resulted in return of ovulation in 90% of participants and 78% conceiving. The miscarriage rate was 18% [64].

However, other studies suggest surprisingly little impact on conception and fertility outcomes. One large multicenter randomized controlled trial involving a 12-week intensive dietary intervention followed by IVF demonstrated a significant weight reduction in the intervention group, but this was not reflected in reproductive outcomes [65]. Live birth rates through IVF and miscarriage rates were not significantly different. The authors did note that the spontaneous pregnancy rates in the intervention group compared to the immediate treatment group were significantly higher. This may, however, have been due to having a longer time to achieve a spontaneous pregnancy, albeit they were then older at the time of IVF [65].

Firstly, lifestyle modification often results in only a modest weight loss. In a general population large-scale disease prevention programs including intensive counseling, support, and changes in diet and exercise, a 4–6 kg weight loss could be achieved but was sufficient to reduce the incidence of diabetes and metabolic syndrome [66]. Unfortunately, achieved weight loss is often regained relatively quickly [61]. It is reported that weight loss through behavior modification and lifestyle change of greater than 10% and sustained for longer than 12 months occurs in only 20% of individuals who start a program [67].

Additionally, lifestyle modification has been attributed to positive effects on the endocrine and metabolic profile of an individual and that this, and not the weight loss, is the cause of the reported improved reproductive outcomes [68]. As such, there is a call for caution on delaying fertility treatment to allow lifestyle modification and weight loss to occur [69].

5.2 Pharmacological agents

Due to the modest weight loss from lifestyle intervention, pharmacotherapy is required as an adjunct to deliver better outcomes. There is good evidence to show that it can be used to help manage hypertension, diabetes, and cardiovascular disease in the obese population when used in addition to not replacing lifestyle intervention.

National and international bodies concur that these pharmacological agents can be used to help with weight loss prior to conceiving in those who are obese or those who are overweight with associated weight-related coexisting conditions [4, 32, 61]. It is important to note, however, that none of these drugs have been studied in men or women before conception and their effects on menstrual cycles, ovulation, or even pregnancy rates are unknown.

Phentermine is a sympathomimetic agent that suppresses appetite. Studies have indicated significant weight loss at 6 months compared to placebo [70]. There are side effects of dry mouth, agitation, insomnia, and tachycardia, and it is not recommended in patients with a history of cardiovascular disease. It is the most commonly used weight loss drug in Australia and the USA.

Orlistat inhibits pancreatic and gastric lipases and so reduces the absorption of dietary fats. It is found to be effective for weight loss [71] but has the side effects of fat malabsorption including steatorrhea, fecal incontinence, and fat-soluble vitamin deficiency [72].

Liraglutide is a glucagon-like peptide-1 agonist and controls hyperglycemia without causing hypoglycemia or weight gain. This drug was initially used to treat type 2 diabetes mellitus but its side effect profile of decreased appetite and subsequent weight loss led to its use as a weight loss agent. Studies demonstrate significant weight loss over placebo and improvement on cardiometabolic parameters [73]. Common side effects are nausea, vomiting, and diarrhea, which are dose related and diminish over time.

Topiramate, an anticonvulsant, has also been used to treat obesity due to the side effect of weight loss and is used as either monotherapy or in combination with phentermine. A naltrexone/bupropion combination has also been demonstrated to provide average weight loss over 12 months [74], and Lorcaserin, a selective 5-hydroxytryptamine 2c receptor agonist, also suppresses appetite with a 3.6% weight loss over a year [75].

All of these agents are contraindicated in pregnancy.

One agent not contraindicated in pregnancy is metformin. Metformin is a biguanide that inhibits hepatic glucose production and increases peripheral tissue sensitivity to insulin, resulting in a reduced circulating insulin and accompanying decreased body weight. Although not intended as a weight loss agent, it is known to reduce weight by 1–2 kg alongside a low-calorie diet and its safety in pregnancy is well studied [61].

Many obese men and women also self-medicate with herbal supplements although their safety and effectiveness have not been demonstrated.

Unfortunately, much like with lifestyle intervention and behavior modification strategies, weight loss is modest at best, and dropout rates with these medications due to time and also side effects typically exceed 30% [76].

5.3 Bariatric surgery

There is an increasing number of bariatric surgical procedures being performed worldwide with nearly 200,000 cases being reported recently [77]. The surgeries vary between restrictive, such as the sleeve gastrectomy or the laparoscopic adjustable gastric banding and the malabsorptive procedures such as biliopancreatic diversion or a mixed restrictive/malabsorptive procedure such as the Roux en Y gastric bypass. Bariatric surgery is considered with morbid obesity (BMI > 40 kg/m2) or with BMI > 35 kg/m2 with concomitant medical conditions exacerbated by obesity [61].

The benefits of bariatric surgery include significant and long-term weight loss. The latest IFSO report demonstrated mean weight loss of 30% at 1 year postsurgery [77], and the Swedish Obese Study [61] showed significant weight reduction was maintained even after 10 years of follow-up [78]. Additionally, bariatric surgery has been shown to improve endocrine and metabolic profiles [61].

In women, bariatric surgery has been shown to improve menstrual regularity [79], correct ovulation [80], improve clinical and biochemical hyperandrogenism along with hyperinsulinemia and glycemic control, and improve both sexual function along with pregnancy rates [81, 82, 83].

In men, bariatric surgery improves hormone profiles by increasing testosterone and decreasing SHBG and estradiol [84]. Studies have not demonstrated an improvement in sperm quality, and in fact there have been case reports that have shown a deterioration on sperm parameters following surgery, likely due to nutritional deficiencies [48, 85]. This is in opposition to findings of longer-term stable sperm parameters following significant weight loss postbariatric surgery [86]. There is no doubt that more research needs to be done in this area to clarify this impact on male fertility.

The obstetric impact of bariatric surgery is profound with the risks of complications such as gestational diabetes, preeclampsia, and fetal macrosomia significantly reduced following surgery when compared to morbidly obese women [61]. Rare surgical complications (bowel obstruction, herniation, band events, and surgical line strictures) have been reported in pregnancy due to intra-abdominal pressure, displacement from the gravid uterus, and even hyperemesis [87, 88]. However, nutritional deficiencies due to malabsorptive-type surgery or noncompliance with long-term supplementation can have a significant effect on fertility and pregnancy outcomes. Deficiencies in iron, vitamin A, vitamin D, vitamin B12, vitamin K, and calcium can lead to maternal complications (e.g., anemia, osteopenia) and fetal complications (e.g., congenital abnormalities) [87]. Although there are no randomized prospective trials addressing time to conception after bariatric surgery, it is suggested to delay pregnancy 1–2 years postsurgery to avoid fetal exposure to nutritional deficiencies from rapid maternal weight loss [87, 89, 90, 91]. A large age and BMI-matched cohort study has demonstrated that the chance of preterm birth and small-for-gestational age (SGA) singletons were greater in women with a history of bariatric surgery than in women without such surgery and that the risk of still birth or neonatal death was slightly higher in the bariatric surgery group as well [92]. The median time from surgery to conception was 1.1 years. There does not appear to be any significant differences in obstetric or perinatal outcomes when comparing the different bariatric surgery procedures [93].

There are, however, studies comparing pregnancies conceived less than 1 year after bariatric surgery to those conceived greater than 1 year after surgery and found no difference in bariatric complications, pregnancy related, or perinatal outcomes [93, 94]. Therefore, when considering advanced age of the woman, the benefits of postponing pregnancy must be balanced against the risk of declining fertility due to age [4, 61].

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6. Conclusion

Obesity is increasing globally in men and women, and the negative impact of overweight and obesity on reproductive health, fertility, pregnancy outcomes, and also transgenerational health is significant. Obesity impairs both natural and assisted conception and has been found to affect endocrine function, oocyte and sperm quality, embryo quality, and also endometrial receptivity and implantation. Pregnancy and live birth rates are lower, and miscarriage rates are higher in the setting of obesity. The metabolic and reproductive health of the offspring is also negatively affected by both maternal and paternal obesity.

Preconceptional weight loss is recommended for all women seeking fertility treatment, firstly through counseling, lifestyle intervention, and behavior modification and then with adjunctive pharmacological agents or bariatric surgery, with a delay to conception of at least 1 year following this. Careful consideration of the benefits of delaying conception for weight loss must be balanced against the possibility of declining fertility due to advancing age of the couple.

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Acknowledgments

Ms. Helen Adams, Librarian, King Edward Memorial Hospital for Women.

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Conflicts of interest

None.

References

  1. 1. World Health Organisation. Obesity. 2018 [updated 2018]. Available from:http://www.who.int/topics/obesity/en/
  2. 2. World Health Organisation. Obesity and overweight. 2018 [updated 2018-02-16]. Available from:http://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
  3. 3. Zegers-Hochschild F, Adamson GD, de Mouzon J, Ishihara O, Mansour R, Nygren K, et al. International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary of ART terminology. Fertility and Sterility. 2009;92(5):1520-1524
  4. 4. Practice Committe of the American Society for Reproductive Medicine. Obesity and reproduction: A committee opinion. Fertility and Sterility. 2015;104(5):1116-1126
  5. 5. Escobar-Morreale HF. Surgical management of metabolic dysfunction in PCOS. Steroids. 2012;77:312-316
  6. 6. Broughton DE, Moley KH. Obesity and female infertility: Potential mediators of obesity’s impact. Fertility and Sterility. 2017;107(4):840-847
  7. 7. Jain A, Polotsky AJ, Rochester D, Berga SL, Loucks T, Zeitlian G, et al. Pulsitile luteinizing hormone amplitude and progesterone metabolite excretion are reduced in obese women. The Journal of Clinical Endocrinology and Metabolism. 2007;92:2468-2473
  8. 8. Wise LA, Rothman KJ, Mikkelsen EM, Sorensen HT, Riis A, Hatch EE. An internet-based prospective study of body size and time-to-pregnancy. Human Reproduction. 2010;25:253-264
  9. 9. Ramlau-Hansen CH, Thulstrup AM, Nohr EA, Bonde JP, Sorensen TI, Olsen J. Subfecundity in overweight and obese couples. Human Reproduction. 2007;22:1634-1637
  10. 10. Gesink Law DC, Maclehose RF, Longnecker MP. Obesity and time to pregnancy. Human Reproduction. 2007;22:414-420
  11. 11. van der Steeg JW, Steures P, Eijkemans MJ, Habbema JD, Hompes PG, Burggraaff JM, et al. Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women. Human Reproduction. 2008;23:324-328
  12. 12. Luke B, Brown MB, Stern JE, Missmer SA, Fujimoto VY, Leach R, et al. Female obesity adversely affects assisted reproductive technology (ART) pregnancy and live birth rates. Human Reproduction. 2011;26(1):245-252
  13. 13. Jungheim ES, Schon SB, Schulte MB, DeUgarte DA, Fowler SA, Tuuli MG. IVF outcomes in obese donor oocyte recipients: A systematic review and meta-analysis. Human Reproduction. 2013;28(10):2720-2727
  14. 14. Esinler I, Bozdag G, Yarali H. Impact of isolated obesity on ICSI outcome. Reproductive Biomedicine Online. 2008;17(4):583-587
  15. 15. Souter I, Baltagi LM, Kuleta D, Meeker JD, Petrozza JC. Women, weight, and fertility: The effect of body mass index on the outcome of superovulation/intrauterine insemination cycles. Fertility and Sterility. 2011;95(3):1042-1047
  16. 16. Shah DK, Missmer SA, Berry KF, Racowsky C, Ginsburg ES. Effect of obesity on oocyte and embryo quality in women undergoing in vitro fertilization. Obstetrics and Gynecology. 2011;118(1):63-70
  17. 17. Moragianni VA, Jones SM, Ryley DA. The effect of body mass index on the outcomes of first assisted reproductive technology cycles. Fertility and Sterility. 2012;98(1):102-108
  18. 18. Pinborg A, Gaarslev C, Hougaard CO, Nyboe Andersen A, Andersen PK, Boivin J, et al. Influence of female bodyweight on IVF outcome: A longitudinal multicentre cohort study of 487 infertile couples. Reproductive Biomedicine Online. 2011;23(4):490-499
  19. 19. Luzzo KM, Wang Q, Purcell SH, Chi M, Jimenez PT, Grindler N, et al. High fat diet induced developmental defects in the mouse: Oocyte meiotic aneuploidy and fetal growth retardation/brain defects. PLoS One. 2012;7(11):e49217
  20. 20. Lane M, Zander-Fox DL, Robker RL, McPherson NO. Peri-conception parental obesity, reproductive health, and transgenerational impacts. Trends in Endocrinology and Metabolism. 2015;26(2):84-90
  21. 21. Wu LL, Dunning KR, Yang X, Russell DL, Lane M, Norman RJ, et al. High-fat diet causes lipotoxicity responses in cumulus-oocyte complexes and decreased fertilization rates. Endocrinology. 2010;151(11):5438-5445
  22. 22. Igosheva N, Abramov AY, Poston L, Eckert JJ, Fleming TP, Duchen MR, et al. Maternal diet-induced obesity alters mitochondrial activity and redox status in mouse oocytes and zygotes. PLoS One. 2010;5(4):e10074
  23. 23. Carrell DT, Jones KP, Peterson CM, Aoki V, Emery BR, Campbell BR. Body mass index is inversely related to intrafollicular HCG concentrations, embryo quality and IVF outcome. Reproductive Biomedicine Online. 2001;3(2):109-111
  24. 24. Metwally M, Cutting R, Tipton A, Skull J, Ledger WL, Li TC. Effect of increased body mass index on oocyte and embryo quality in IVF patients. Reproductive Biomedicine Online. 2007;15:532-538
  25. 25. Leary C, Leese HJ, Sturmey RG. Human embryos from overweight and obese women display phenotypic and metabolic abnormalities. Human Reproduction. 2015;30(1):122-132
  26. 26. Jungheim ES, Macones GA, Odem RR, Patterson BW, Lanzendorf SE, Ratts VS, et al. Associations between free fatty acids, cumulus oocyte complex morphology and ovarian function during in vitro fertilization. Fertility and Sterility. 2011;95(6):1970-1974
  27. 27. Magarinos MP, Sanchez-Margalet V, Kotler M, Calvo JC, Varone CL. Leptin promotes cell proliferation and survival of trophoblastic cells. Biology of Reproduction. 2007;76(2):203-210
  28. 28. Fedorcsak P, Dale PO, Storeng R, Ertzeid G, Bjercke S, Oldereid N, et al. Impact of overweight and underweight on assisted reproduction treatment. Human Reproduction. 2004;19(11):2523-2528
  29. 29. Spandorfer SD, Kump L, Goldschlag D, Brodkin T, Davis OK, Rosenwaks Z. Obesity and in vitro fertilization: Negative influences on outcome. The Journal of Reproductive Medicine. 2004;49(12):973-977
  30. 30. Dechaud H, Anahory T, Reyftmann L, Loup V, Hamamah S, Hedon B. Obesity does not adversely affect results in patients who are undergoing in vitro fertilization and embryo transfer. European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2006;127(1):88-93
  31. 31. Bellver J, Ayllon Y, Ferrando M, Melo M, Goyri E, Pellicer A, et al. Female obesity impairs in vitro fertilization outcome without affecting embryo quality. Fertility and Sterility. 2010;93(2):447-454
  32. 32. Brewer CJ, Balen AH. The adverse effects of obesity on conception and implantation. Reproduction. 2010;140(3):347-364
  33. 33. Bellver J, Martinez-Conejero JA, Labarta E, Alama P, Melo MA, Remohi J, et al. Endometrial gene expression in the window of implantation is altered in obese women especially in association with polycystic ovary syndrome. Fertility and Sterility. 2011;95(7):2335-2341. 41 e1-8
  34. 34. Bellver J, Melo MA, Bosch E, Serra V, Remohi J, Pellicer A. Obesity and poor reproductive outcome: The potential role of the endometrium. Fertility and Sterility. 2007;88(2):446-451
  35. 35. Alvarez C, Alonso-Muriel I, Garcia G, Crespo J, Bellver J, Simon C, et al. Implantation is apparently unaffected by the dopamine agonist cabergoline when administered to prevent ovarian hyperstimulation syndrome in women undergoing assisted reproduction treatment: A pilot study. Human Reproduction. 2007;22(12):3210-3214
  36. 36. DeUgarte DA, DeUgarte CM, Sahakian V. Surrogate obesity negatively impacts pregnancy rates in third-party reproduction. Fertility and Sterility. 2010;93(3):1008-1010
  37. 37. Wattanakumtornkul S, Damario MA, Stevens Hall SA, Thornhill AR, Tummon IS. Body mass index and uterine receptivity in the oocyte donation model. Fertility and Sterility. 2003;80(2):336-340
  38. 38. Loveland JB, McClamrock HD, Malinow AM, Sharara FI. Increased body mass index has a deleterious effect on in vitro fertilization outcome. Journal of Assisted Reproduction and Genetics. 2001;18(7):382-386
  39. 39. Wang JX, Davies MJ, Norman RJ. Obesity increases the risk of spontaneous abortion during infertility treatment. Obesity Research. 2002;10(6):551-554
  40. 40. Rittenberg V, Seshadri S, Sunkara SK, Sobaleva S, Oteng-Ntim E, El-Toukhy T. Effect of body mass index on IVF treatment outcome: An updated systematic review and meta-analysis. Reproductive Biomedicine Online. 2011;23(4):421-439
  41. 41. Donnino MW, Rittenberger JC, Gaieski D, Cocchi MN, Giberson B, Peberdy MA, et al. The development and implementation of cardiac arrest centers. Resuscitation. 2011;82(8):974-978
  42. 42. Bellver J, Rossal LP, Bosch E, Zuniga A, Corona JT, Melendez F, et al. Obesity and the risk of spontaneous abortion after oocyte donation. Fertility and Sterility. 2003;79(5):1136-1140
  43. 43. Bellver J, Albert C, Labarta E, Pellicer A. Early pregnancy loss in women stimulated with gonadotropin-releasing hormone antagonist protocols according to oral contraceptive pill pretreatment. Fertility and Sterility. 2007;87(5):1098-1101
  44. 44. Metwally M, Ong KJ, Ledger WL, Li TC. Does high body mass index increase the risk of miscarriage after spontaneous and assisted conception? A meta-analysis of the evidence. Fertility and Sterility. 2008;90(3):714-726
  45. 45. Metwally M, Saravelos SH, Ledger WL, Li TC. Body mass index and risk of miscarriage in women with recurrent miscarriage. Fertility and Sterility. 2010;94(1):290-295
  46. 46. MacDonald AA, Herbison GP, Showell M, Farquhar CM. The impact of body mass index on semen parameters and reproductive hormones in human males: A systematic review with meta-analysis. Human Reproduction Update. 2010;16(3):293-311
  47. 47. McPherson NO, Lane M. Male obesity and subfertility, is it really about increased adiposity? Asian Journal of Andrology. 2015;17(3):450-458
  48. 48. Sermondade N, Dupont C, Faure C, Boubaya M, Cedrin-Durnerin I, Chavatte-Palmer P, et al. Body mass index is not associated with sperm-zona pellucida binding ability in subfertile males. Asian Journal of Andrology. 2013;15(5):626-629
  49. 49. Lewis SE, John Aitken R, Conner SJ, Iuliis GD, Evenson DP, Henkel R, et al. The impact of sperm DNA damage in assisted conception and beyond: Recent advances in diagnosis and treatment. Reproductive Biomedicine Online. 2013;27(4):325-337
  50. 50. Zhao J, Zhai L, Liu Z, Wu S, Xu L. Leptin level and oxidative stress contribute to obesity-induced low testosterone in murine testicular tissue. Oxidative Medicine and Cellular Longevity. 2014;2014:190945
  51. 51. Duale N, Steffensen IL, Andersen J, Brevik A, Brunborg G, Lindeman B. Impaired sperm chromatin integrity in obese mice. Andrology. 2014;2(2):234-243
  52. 52. Palmer NO, Bakos HW, Owens JA, Setchell BP, Lane M. Diet and exercise in an obese mouse fed a high-fat diet improve metabolic health and reverse perturbed sperm function. American Journal of Physiology. Endocrinology and Metabolism. 2012;302(7):E768-E780
  53. 53. Jia YF, Feng Q, Ge ZY, Guo Y, Zhou F, Zhang KS, et al. Obesity impairs male fertility through long-term effects on spermatogenesis. BMC Urology. 2018;18(1):42
  54. 54. Tamler R. Diabetes, obesity, and erectile dysfunction. Gender Medicine. 2009;6(Suppl 1):4-16
  55. 55. Loche E, Ozanne SE. Non-genetic transmission of obesity—It’s in your epigenes. Trends in Endocrinology and Metabolism. 2016;27(6):349-350
  56. 56. Huypens P, Sass S, Wu M, Dyckhoff D, Tschop M, Theis F, et al. Epigenetic germline inheritance of diet-induced obesity and insulin resistance. Nature Genetics. 2016;48(5):497-499
  57. 57. Fullston T, Ohlsson Teague EM, Palmer NO, DeBlasio MJ, Mitchell M, Corbett M, et al. Paternal obesity initiates metabolic disturbances in two generations of mice with incomplete penetrance to the F2 generation and alters the transcriptional profile of testis and sperm microRNA content. The FASEB Journal. 2013;27(10):4226-4243
  58. 58. Tunc O, Tremellen K. Oxidative DNA damage impairs global sperm DNA methylation in infertile men. Journal of Assisted Reproduction and Genetics. 2009;26(9-10):537-544
  59. 59. Chen Q, Yan M, Cao Z, Li X, Zhang Y, Shi J, et al. Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder. Science. 2016;351(6271):397-400
  60. 60. Soubry A, Murphy SK, Wang F, Huang Z, Vidal AC, Fuemmeler BF, et al. Newborns of obese parents have altered DNA methylation patterns at imprinted genes. International Journal of Obesity. 2015;39(4):650-657
  61. 61. Mahutte N, Kamga-Ngande C, Sharma A, Sylvestre C. Obesity and reproduction. Journal of Obstetrics and Gynaecology Canada. 2018;40(7):950-966
  62. 62. Legro RS, Dodson WC, Kunselman AR, Stetter CM, Kris-Etherton PM, Williams NI, et al. Benefit of delayed fertility therapy with preconception weight loss over immediate therapy in obese women with PCOS. The Journal of Clinical Endocrinology and Metabolism. 2016;101(7):2658-2666
  63. 63. Espinos JJ, Polo A, Sanchez-Hernandez J, Bordas R, Pares P, Martinez O, et al. Weight decrease improves live birth rates in obese women undergoing IVF: A pilot study. Reproductive Biomedicine Online. 2017;35(4):417-424
  64. 64. Clark AM, Thornley B, Tomlinson L, Galletley C, Norman RJ. Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Human Reproduction. 1998;13(6):1502-1505
  65. 65. Einarsson S, Bergh C, Friberg B, Pinborg A, Klajnbard A, Karlstrom PO, et al. Weight reduction intervention for obese infertile women prior to IVF: A randomized controlled trial. Human Reproduction. 2017;32(8):1621-1630
  66. 66. Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. The New England Journal of Medicine. 2001;344(18):1343-1350
  67. 67. Wing RR, Hill JO. Successful weight loss maintenance. Annual Review of Nutrition. 2001;21:323-341
  68. 68. Palomba S, Falbo A, Valli B, Morini D, Villani MT, Nicoli A, et al. Physical activity before IVF and ICSI cycles in infertile obese women: An observational cohort study. Reproductive Biomedicine Online. 2014;29(1):72-79
  69. 69. Meldrum DR. Introduction: Obesity and reproduction. Fertility and Sterility. 2017;107(4):831-832
  70. 70. Li Z, Maglione M, Tu W, Mojica W, Arterburn D, Shugarman LR, et al. Meta-analysis: Pharmacologic treatment of obesity. Annals of Internal Medicine. 2005;142(7):532-546
  71. 71. Apovian CM, Aronne LJ, Bessesen DH, McDonnell ME, Murad MH, Pagotto U, et al. Pharmacological management of obesity: An endocrine society clinical practice guideline. The Journal of Clinical Endocrinology and Metabolism. 2015;100(2):342-362
  72. 72. Lee PC, Dixon J. Pharmacotherapy for obesity. Australian Family Physician. 2017;46(7):472-477
  73. 73. Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. The New England Journal of Medicine. 2015;373(1):11-22
  74. 74. Greenway FL, Fujioka K, Plodkowski RA, Mudaliar S, Guttadauria M, Erickson J, et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): A multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2010;376(9741):595-605
  75. 75. Smith SR, Weissman NJ, Anderson CM, Sanchez M, Chuang E, Stubbe S, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. The New England Journal of Medicine. 2010;363(3):245-256
  76. 76. Fabricatore AN, Wadden TA, Moore RH, Butryn ML, Gravallese EA, Erondu NE, et al. Attrition from randomized controlled trials of pharmacological weight loss agents: A systematic review and analysis. Obesity Reviews. 2009;10(3):333-341
  77. 77. Higa K, Himpens J, Welbourn R, Dixon J, Kinsman R, Walton P. Third IFSO Global Registry Report 2017. Updated August 2017. Available from:http://www.ifso.com/wp-content/themes/ypo-theme/pdfs/final-3rd-ifso-report-21st-august-2017.pdf
  78. 78. Sjostrom L, Lindroos AK, Peltonen M, Torgerson J, Bouchard C, Carlsson B, et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. The New England Journal of Medicine. 2004;351(26):2683-2693
  79. 79. Teitelman M, Grotegut CA, Williams NN, Lewis JD. The impact of bariatric surgery on menstrual patterns. Obesity Surgery. 2006;16(11):1457-1463
  80. 80. Tan O, Carr BR. The impact of bariatric surgery on obesity-related infertility and in vitro fertilization outcomes. Seminars in Reproductive Medicine. 2012;30(6):517-528
  81. 81. Legro RS, Dodson WC, Gnatuk CL, Estes SJ, Kunselman AR, Meadows JW, et al. Effects of gastric bypass surgery on female reproductive function. The Journal of Clinical Endocrinology and Metabolism. 2012;97(12):4540-4548
  82. 82. Marceau P, Kaufman D, Biron S, Hould FS, Lebel S, Marceau S, et al. Outcome of pregnancies after biliopancreatic diversion. Obesity Surgery. 2004;14(3):318-324
  83. 83. Musella M, Milone M, Bellini M, Sosa Fernandez LM, Leongito M, Milone F. Effect of bariatric surgery on obesity-related infertility. Surgery for Obesity and Related Diseases. 2012;8(4):445-449
  84. 84. Reis LO, Zani EL, Saad RD, Chaim EA, de Oliveira LC, Fregonesi A. Bariatric surgery does not interfere with sperm quality—A preliminary long-term study. Reproductive Sciences. 2012;19(10):1057-1062
  85. 85. di Frega AS, Dale B, Di Matteo L, Wilding M. Secondary male factor infertility after Roux-en-Y gastric bypass for morbid obesity: Case report. Human Reproduction. 2005;20(4):997-998
  86. 86. Legro RS, Kunselman AR, Meadows JW, Kesner JS, Krieg EF, Rogers AM, et al. Time-related increase in urinary testosterone levels and stable semen analysis parameters after bariatric surgery in men. Reproductive Biomedicine Online. 2015;30(2):150-156
  87. 87. Guelinckx I, Devlieger R, Vansant G. Reproductive outcome after bariatric surgery: A critical review. Human Reproduction Update. 2009;15(2):189-201
  88. 88. Hezelgrave NL, Oteng-Ntim E. Pregnancy after bariatric surgery: A review. Journal of Obesity. 2011;2011:501939
  89. 89. Beard JH, Bell RL, Duffy AJ. Reproductive considerations and pregnancy after bariatric surgery: Current evidence and recommendations. Obesity Surgery. 2008;18(8):1023-1027
  90. 90. Monson M, Jackson M. Pregnancy after bariatric surgery. Clinical Obstetrics and Gynecology. 2016;59(1):158-171
  91. 91. American Dietetic A, American Society of N, Siega-Riz AM, King JC. Position of the American Dietetic Association and American Society for Nutrition: Obesity, reproduction, and pregnancy outcomes. Journal of the American Dietetic Association. 2009;109(5):918-927
  92. 92. Johansson K, Cnattingius S, Naslund I, Roos N, Trolle Lagerros Y, Granath F, et al. Outcomes of pregnancy after bariatric surgery. The New England Journal of Medicine. 2015;372(9):814-824
  93. 93. Sheiner E, Balaban E, Dreiher J, Levi I, Levy A. Pregnancy outcome in patients following different types of bariatric surgeries. Obesity Surgery. 2009;19(9):1286-1292
  94. 94. Kjaer MM, Nilas L. Timing of pregnancy after gastric bypass-a national register-based cohort study. Obesity Surgery. 2013;23(8):1281-1285

Written By

Tamara Hunter and Roger Hart

Submitted: May 22nd, 2018 Reviewed: August 13th, 2018 Published: December 31st, 2018