The impact of obesity on fertility and pregnancy Dr : Reem Murad

Obesity & Reproductive Health Amenorrhea anovulation sub fertility infertility is increasingly occurring with higher body weight

Obesity is strongly associated with PCOS obese women at risk of infertility : threefold increased risk of lifetime to be infertile as a normal woman

Increase in BMI reduces the chance of conception in ovulatory women and affects the outcome of ovulation induction treatment. Obese women undergoing IVF require higher doses of gonadotrophins, respond poorly to ovarian stimulation and have fewer oocytes harvested. Obesity is associated with lower fertilization rates, poor quality embryos and higher miscarriage rates. Weight loss in these women improves their reproductive outcomes; however, in order for this to be effective it has to be gradual and sustained.

OBESITY & ASSISTED REPRODUCTION (ART) 1. poorer prognosis with Assisted Reproduction 2. Pregnancy Rates in ART halved for women with BMI > 35 kg/m2 have a lower chance of pregnancy following In Vitro Fertilization require higher doses of gonadotropins and have an increased miscarriage rate

Impact of Obesity on Assisted Reproduction

Obesity during pregnancy is associated with numerous maternal and perinatal risks Managing these problems, and potentially reducing their risk

It is not clear whether obesity is a direct cause of adverse pregnancy outcome or whether the association between obesity and adverse pregnancy outcome is due to factors that are shared characteristics of both entities.

a causal association between maternal obesity and several pregnancy complications the risks increase with increasing obesity The mechanism related to the endocrine milieu associated with obesity (increased levels of insulin, androgens, and leptin) adipose tissue is an active endocrine organ and a source of proinflammatory cytokines (adipokines), which may lead to vascular endothelial dysfunction in the mother and placenta and result in adverse pregnancy outcome

Maternal prepregnancy BMI for the first and second pregnancies was determined and compared to pregnancy outcome Compared to women whose BMI changed -1.0 to +0.9 units, a three unit increase in BMI (about 9 kg for a woman of average height) between pregnancies was associated with significantly increased risks of preeclampsia, gestational hypertension, gestational diabetes, cesarean delivery, large-for-gestational age infant, and stillbirth in the second pregnancy

The increase in risk was related linearly to the amount of weight gained in the interpregnancy interval, and was also noted in women who gained weight but whose BMI remained in the normal range. The effect of a modest to large weight loss (more than -1 BMI units or at least 3 kg) between pregnancies could not be evaluated because there were too few women in this subgroup

PREVALENCE OF OBESITY DURING PREGNANCY The prevalence of obesity during pregnancy varies widely The prevalence has increased in concordance with the increased prevalence of obesity in the general population

FERTILITY AND EARLY PREGNANCY Subfertility  — association between increased BMI and subfertility. weight reduction in obese, infertile women was associated with an increase in the frequency of ovulation and the likelihood of pregnancy. Subfertility in obese women is most commonly related to - ovulatory dysfunction - and, in some is related to polycystic ovary syndrome (PCOS)

Even ovulatory women, increasing obesity is associated with decreasing spontaneous pregnancy rates and increased time to pregnancy The mechanism may be related to adverse effects of elevated insulin levels on ovarian function

Obesity may also have a negative impact on the outcome of treatment of infertility. poorer outcomes of infertility treatment in these women (eg, insufficient follicular development, lower oocyte counts) - higher doses of ovulation inducing agents need to be used Obesity affect the outcome of in vitro fertilization (IVF).

The risk of unsuccessful IVF/ICSI increases with increasing BMI and may be related to oocyte quality, ovarian function, endometrial quality, or a combination of these factors overweight women had a significantly lower clinical pregnancy rate and live-birth rate and a significantly higher miscarriage rate -ICSI :Intracytoplasmic Sperm Injection -IVF : in vitro fertilization

weight loss in obese subfertile women can lead to favorable hormonal changes and improvement in fertility There are data that Metformin treatment of obese women with infertility due to PCOS induces ovulation, supporting the concept that insulin resistance impairs normal oocyte development

Interpregnancy weight loss a decrease in weight from obese to normal between first and second pregnancies reduces the risk of cesarean delivery and large for gestational age infants Interpregnancy weight loss was not associated with an increased risk of small for gestational age infants, except in women with a greater than 8 unit reduction in BMI

Spontaneous abortion   women with BMI ≥30 kg/m 2 are at increased risk of miscarriage when compared with women with normal BMI Miscarriage risk was not increased in women undergoing IVF.

The increased risk may be because obese women often have PCOS or isolated insulin resistance, which have been associated with a higher frequency of early pregnancy loss An unfavorable hormonal environment resulting in poorer endometrial receptivity likely plays a role treatment with Metformin in women with PCOS reduces the frequency of spontaneous abortion?

Gestational and pregestational diabetes In the United States, routine screening for gestational diabetes The incidence of gestational diabetes in pregnancies of obese gravidas is increased,l The magnitude of this risk is positively correlated with increases in maternal weight type 2 diabetes mellitus is one of the most common medical complications of the obese gravida

The increased risk of type 2 diabetes is related to increase in insulin resistance in the obese state screen obese gravidas in the first trimester for undiagnosed pregestational diabetes Glucose intolerance resolves postpartum obese women with a history of gestational diabetes have a two-fold increased prevalence of subsequent type 2 diabetes

Weight loss and healthy lifestyle can help to prevent type 2 diabetes and also appears to reduce the risk of gestational diabetes weight gain between pregnancies and between age 18 and pregnancy increase the risk of developing gestational diabetes Excessive weight gain in early to mid pregnancy is associated with impaired glucose tolerance or gestational diabetes

Pregnancy associated hypertension maternal weight is independent risk factors for preeclampsia, as well as other hypertensive disorders women who underwent bariatric surgery suggest that weight loss significantly reduces the risk of preeclampsia obesity-related cardiovascular risk –are responsible for the increased incidence of preeclampsia in obese gravidas : insulin resistance Hyperlipidemia subclinical inflammation

routine low-dose aspirin therapy is not recommend in the absence of other risk factors for reducing developing preeclampsia.

Preterm birth   obesity is not associated with an increased risk of spontaneous preterm birth <37 weeks after adjustment for confounders (race, age, parity, smoking) an increased risk of preterm birth in obese gravidas prematurity was primarily associated with obesity-related medical and antenatal complications, rather than an intrinsic predisposition to spontaneous preterm birth

Postterm pregnancy   an association between obesity and postterm pregnancy Increased prolonged pregnancy in obese women ..The mechanisms ?

Multifetal pregnancy   increased incidence of dizygotic twin gestation (not monozygotic) has been reported may be attributed to elevated follicle-stimulating hormone (FSH) levels

Urinary tract infection increase in risk of urinary tract infections

Obstructive sleep apnea Obstructive sleep apnea (OSA) is a rare but serious obesity-related disorder. OSA may be precipitated or exacerbated during pregnancy and may be associated with hypertensive disorders during pregnancy and impaired fetal growth .

Labor Obese women appear to have a longer first stage of labor than normal weight women Labor induction is more common among obese women than among their lean counterparts Induction failure is also more common in obese women

Vaginal birth after cesarean delivery vaginal birth after cesarean delivery is less successful in obese gravidas

Cesarean delivery   prepregnancy obesity increases the probability of both elective and emergency cesarean delivery Excessive weight gain before and during pregnancy also increases the risk of cesarean delivery

Cesarean delivery   obesity may lead to dystocia due to increased soft tissue deposition in the maternal pelvis. Another contributor to increased cesarean risk may be abnormalities during fetal heart rate assessment

Cesarean delivery   Cesarean delivery in the obese gravida is associated with: emergency delivery prolonged incision to delivery interval blood loss >1000 mL longer operative times wound infection Thromboembolism endometritis

Anesthetic management Evaluation by an anesthesiologist prior to labor is recommended for all obese parturients because of the higher risk of anesthetic complications. a higher initial epidural failure rate, a higher rate of difficult intubation more inadvertent dural puncture a higher frequency of multiple attempts at placement and higher rates of hypotension and fetal rate decelerations Early placement of an epidural or intrathecal catheter may obviate the need for general anesthesia .

intrapartum complications related to macrosomia such as shoulder dystocia malpresentation, hemorrhage and fourth degree laceration increased incidence of intrapartum fetal heart rate abnormalities cord accidents meconium stained amniotic fluid

POSTPARTUM   Obese women spend more days in the hospital postpartum than leaner women. Prolonged hospitalization was due to postpartum complications

Infection higher risk for postpartum infection (wound, episiotomy, endometritis) Poor vascularity of subcutaneous adipose tissue and formation of seromas and hematomas account for the increased risk of wound infection.

Postpartum hemorrhage postpartum hemorrhage due to : an increased frequency of macrosomia or because the relatively large volume of distribution related to obesity may result in reduced bioavailability of uterotonic agents at standard doses.

Breastfeeding increased risk of failure to initiate lactation and decreased duration of lactation alterations in the hypothalamic-pituitary-gonadal axis and fat metabolism have been implicated overweight/obese women have a lower prolactin response to suckling in the first week postpartum, which may contribute to early lactation failure

PERINATAL OUTCOME Congenital anomalies   : a small increase in some congenital anomalies, and the risk may increase with increasing maternal weight The mechanism for the association is not known, but is likely related to an altered nutritional milieu for fetal development, including hyperinsulinemia.

Perinatal mortality Experience more stillbirths have higher rates of diabetes and hypertension metabolic changes associated with obesity (hyperlipidemia with reduced prostacyclin production), decreased awareness of fetal movement, and nocturnal apnea with transient oxygen desaturation. neonatal death, largely from pregnancy complications or disorders leading to preterm birth

  play an important role in determining infant birth weight increased risk of delivering a large for gestational age infant Two potential sequelae of being large for gestational age are: Shoulder dystocia Predisposition to obesity later in life

  obesity, diabetes, and hypertension were more common among mothers of children with autism increased risk of intellectual disability in offspring

RECOMMENDATIONS   Preconception weight reduction and limitation of maternal weight gain in obese gravidas through diet and exercise are recommended.

Treatment For Infertility in Obesity Life – Style & Nutrition Changes Diet Exercise Psychological Counseling Surgical Intervention Bariatric surgery ART - IUI - IVF - ICSI Pharmacological Even 5% Weight loss improves fertility outcome Impacts Fertility Outcomes

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