Obesity and pregnancy

Erin KeelyMary-Anne Doyle

Objectives• Discuss the impact that obesity has on reproductive hormones and how it

may lead to subfertility and infertility in both men and women • Describe the investigations recommended to determine the cause of

subfertility and infertility associated with obesity• Discuss the management of obesity related infertility• Describe the benefits of pre-conception counselling and the role of lifestyle

modification for obese women considering pregnancy• Describe weight gain goals for pregnant women and how obesity impacts on

these targets• Identify barriers and challenges obese women encounter during pre-natal

care• Describe the obesity related co-morbidities specific to pregnancy• Identify and explain the pathophysiology of common medical complications

of pregnancy related to obesity. • Briefly state the management of pregnancy‐related medical complications

potential. • Classify and describe the potential impact of obesity on fetal and maternal

well being during labor and delivery, including risks of surgery and anesthesia.

• Relate maternal obesity to fetal and neonatal risks of Intra‐uterine growth retardation (IUGR), macrosomia, injury from labor complications, etc…

• List and describe the interventions recommended to prevent fetal/neonatal complications related to maternal obesity.

Obesity in women ages 20-39 the US(NHANES 1999-2002)

All Non-hispanic white

Non-hispanic black

Mexican American

BMI >25

54.5% 49.0% 70.3% 61.8%

BMI >30

29.1% 24.9% 46.6% 31.2%

BMI >40

5.6% 4.2% 11.8% 5.5%

Hedley, JAMA 2004;291:2847-50

Saravamakumar Anaesthesia 2006

Obesity rates in women 16-44 yrs increased from 1993 to 2002

• BMI > 30• 12% to 18%

• BMI > 40• 1.2% to 2.2%

Bias towards Obese Pregnant Women

• Survey of obstetrics provided in the Ottawa area

• 11% agreed to making insensitive comments to obese pregnant women

• 31% agreed to making derogatory comments about obese pregnant women to colleagues

• 66% believe more derogatory comments are made about obese pregnant women vs non –obese pregnant women

Grohman et al, Obstetric Medicine 2012

DON’T BE THAT

PERSON!!

Obstetrical risks and obesity• Infertility• Failure of contraception• Gestational or type 2 diabetes

• Preeclampsia• Risk of c-section• Surgical complications

• Wound• Respiratory• thrombosis

• First trimester loss• Late pregnancy loss• Macrosomia• Congenital anomalies

• Neural tube• Cardiac• More difficult to diagnose

• Decreased breast feeding

Case• 32 year old, lawyer, never pregnant, married for

2 years and trying to conceive

• Menarche at age 13, with irregular cycles for first 2 years, then became regular for 3 years

• She moved away for university and gained 23 kg

• Her menses became irregular and she had increased facial hair and acne

• She took an oral contraceptive for 10 years but stopped 2 years ago. It regulated her menses and reduced her hair growth and acne

• Since stopping, her menses are very irregular, missing up to several months at a time, with heavy bleeding when they do occur.

Case• Social History:

• She has a busy law practice with little time for exercise and acknowledges that she makes poor dietary choices.

• She has tried and failed several popular diet programs.

• She is stressed, tired and has labile moods

• Family History• Father 65 yrs old with hypertension, type 2 diabetes

• Mother, 63, smoker, CAD, hypertension

Case

Physical Exam:• BP 142/86, BMI 36 kg/m2, waist 105

cm

• Facial and upper back acne

• Severe hirsutism with coarse upper lip hair, sideburns, chest hair, pubic hair reaching naval and inner thighs

• Abdominal striae

• Acanthosis nigricans

Cause of Infertility?

Obesity and Fertility• Infertility defined as the absence of conception after one

year of unprotected intercourse.

• Estimated to affect 11.5% to 15.7 % for fertile couples.

• Obese woman are 3x more likely to suffer infertility compared with woman with a normal BMI.

• Central obesity had an impact on conception.• WHR>0.8 -30% less likely to conceive than those with WHR<0.7

Fertility

30%

30%10%

25%5%

Causes of Infertility

MaleFemaleCombinedUnexplainedOther

Department of Health UK, June 2009

• 4,412 couples from the 2009-2010 Canadian Community Health Survey

• Up to 16% of couples where the woman is age 18-to-44 are experiencing infertility — almost a 2-fold increase since 1992.

• In 1984, about 5% of couples with a female partner age 18-to-29 were infertile.

• By 2009-10, the prevalence for the same age group was as high as 13.7%.

• Obesity rates are also climbing:• In 2007-09, 21% of women ages 20 to 39 in Canada were obese vs 4% in 1981.

Hum Reprod. 2012 Mar; 27(3): 738–746.

Back to the case. . .

Important Diagnoses to Exclude

Late Onset CAH

Cushing’s Sydnrome

Thyroid Disease

Hypothalamic oligo/amenorrhea

Androgen Secreting Tumour

Hyperprolactinemia

Hypopituitarism

Premature Ovarian Failure

Investigations• -hCG • Prolactin• LH & FSH• Testosterone• DHEAS• 17-OH Progesterone• TSH• Screening for excess cortisol

PCOS is Prevalent!

Affects 8-12% of women depending on criteria used.

Most common cause of oligo-anovulatory infertility.

65-80% of women with hirsutism have PCOS

50-70% overweight or obese

50-70% of women with PCOS have IR

Clinical Features of PCOS

• Hirsutism• Acne• Male Pattern Hair Loss

Hyperandrogenism

• Oligomenorrhea/Amenorrhea• Dysfunctional Uterine bleeding• FERTILITY

Fertility & Menstrual Irregularities

Pathophysiology

NEJM 2005 (352)

PCOS and Obesity• Obesity strongly associated with PCOS

• 50-70% of cases obesity is present• 30% of morbidly obese women vs only 5% of the lean population

• Obese PCOS had 7-10 fold increase in conversion rate from normal glucose tolerance to IGT or T2DM

• Increased prevalence of metabolic syndrome in obese patients with PCOS (3.2% to 52.3%)

• Many features of PCOS are completely resolved with:• Weight loss through lifestyle intervention, bariatric surgery

BJOG 2006 (113)

Obesity, Hyperinsulinemia and PCOS

PCOS

HYPERINSULINEMIA

+

Central Obesity

Amplification actions of LH

Ovarian androgenProduction ↑

+

SHBG ↓

+

↑ FreeTestosterone

ANOVULATION

More FSH needed for ovulation induction

Greater tendency for multifollicular response

Inferior pregnancy and miscarriage

HIRSUTISM

ACNEBest Pract Res Clin Obs Gyn 2008 (22)

Obesity and Fertility in Ovulatory Women

• The probability of a spontaneous pregnancy declined linearly with a body mass index (BMI) over 29 kg/m2.

• Women with a high BMI had a 4% lower pregnancy rate per kg/m2 increase.

Human Reproduction Vol.23, No.2 pp. 324–328, 2008

Female obesity and Fertility• Impaired ovulation

• Oocyte development

• Embryonic development

• Endometrial development

• Implantation

• Miscarriage

• Congenital abnormalities

• Psychological and sociological factors

• Reduction in sexual frequency

• Sexual dysfunction

Role for Fertility treatment?

Obesity and Fertility Treatment

Obesity and Assisted Reproductive Therapy (ART)

• Obesity has been shown to impair outcome of ART.

• Increase in BMI by 1 unit results in ~15% reduction in pregnancy with ART.1

• Higher gonadotropins required, lower ovulation, decrease fertilization, reduced oocyte retrieval, reduced oocyte quality.2

1. J Assisted Repro Genetics (2004); 21:431.2. Reproduction (2010); 140: 347.

Systematic Review

• BMI>25 kg/m2 had a lower chance of pregnancy after IVF • OR 0.71 (95% CI 0.62-0.81)

• BMI >30 kg/m2 required more gonadotrophin for ovarian stimulation• WMD 316.94 (95% CI 156.47-567.40)

• BMI>30 kg/m2 had increased risk of miscarriage• OR 1.53 (95% CI 1.27-1.84)

Human Reproduction Update 2007; 13: 443.

Weight loss and Fertility

Role of Weight Loss ?

Dietary and Lifestyle

Bariatric Surgery

Weight loss and Pregnancy• Weight loss of ~5% in obese women with PCOS leads to

↑spontaneous ovulation rates and pregnancy.

Prospective Cohort Study with various causes of infertility.• Obese women who completed 6-month lifestyle

intervention.

• Mean weight loss 10kg vs 1kg • Pregnancy rate 77% and Live birth rate of 67%• 90% of anovulatory women intervention group were ovulating at

study end.

Human Repro 1998; 13:1502.

Retrospective Cohort Study

• Overweight patients with• a BMI of 33 • documented infertility of >12

months

• “Meaningful weight loss” of >10%

• Success rates similar to most IVF programs and should be considered as a primary intervention

Preg-nancy

Live Birth Rates

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

<10%>10%

Fertil Steril. 2014 May;101(5):1400-3. doi: 10.1016/j.fertnstert.2014.01.036. Epub 2014 Feb 26

Dietary and Lifestyle Changes• Systematic Review (2014):

• 4/7 studies reported statistically significant improvement in pregnancy rates and/or live births in intervention group

• Significant differences in interventions and various degrees of weight loss

• Other benefits:• Regulation of menstrual cycle• Reduction in ART cycles required to achieve pregnancy

• Conclusions: Prospective randomized controlled trials are required to establish efficacious evidence-based guidelines for weight loss interventions in overweight/obese women.

Obesity Reviews 2014; 15: 839

Mechanism of improved fertility?

Improved Fertility

↓ insulin resistance

↓ androgen levels

Stabilization of sex hormones

↑psychological factors

ROLE FOR BARIATRIC SURGERY?

Bariatric SurgeryRemission of diabetes

Normalization of blood pressure

Improved lipid profiles

Resolution of obstructive sleep apnea

Pregnancy? Live births?

Pregnancy after Bariatric Surgery• 70-80% of patients seeking bariatric surgery are women of

childbearing age.

• Future pregnancy identified as important in 30% of women of reproductive age undergoing bariatric surgery.

• “Fertility performance” is improved following bariatric surgery.• ~70-80% of ovulatory disorders resolve post-bariatric surgery

• Radical weight loss may have adverse effect• i.e hypogonadrotropic hypogonadism

Hormonal changes with bariatric surgery

Curr Opin 2012; 22: 248

Bariatric Surgery and Pregnancy• Literature suggests improvement in pregnancy rates after

bariatric surgery but lack of good quality prospective studies to evaluate this.

Retrospective Cohort:• 783 women biliopancreatic diversion • Pre: mean BMI = 47kg/m2 • Post: mean BMI = 30 kg/m2

• 47% women who were unable to become pregnant pre-operatively achieved spontaneous pregnancy post-bariatric surgery.

Obes Surg 2004; 14:318

IVF Outcomes and Miscarriage rates• Lack of literature evaluating the impact or surgical weight

loss on IVF outcomes

Miscarriage:• Small cohort study (9 patients) post gastric-banding

• Decrease in miscarriage rates• 6/18 pregnancies pre-surgery• 1/13 pregnancies post-surgery

Curr Opinion 2010; 22: 248Obstet Gynec Scand 1995; 74:42.

Miscarriage Rates

Cohort of 1136 women• post biliopancreatic diversion.1

Miscarriage rates: • 17% pre-surgery vs 11% post-surgery

• Cohort of 700 women2

• Showed no difference in self-reported miscarriage rates.

1. Obes Surg 1995; 5: 3082. Obes Surg 2004; 14: 318

Other considerations• Generally advised to delay pregnancy 12-18 months after

surgery• ?Increase risk of low birth weight, IUGR, NTD• Lack of evidence to support this.

• Concerns that patients may not absorb OCP as well so they should consider additional forms of contraception.

• Nutritional Deficiencies?• Bariatric surgery associated with micronutrient deficiencies

Nutritional Deficiencies• Advised to take a MVI supplement

• Calcium: Ca Citrate 2000 mg od/Vitamin D >2000IU

• Fe deficiency Anemia: Fe suppl 40-65 mg/day

• B12 deficiency: 10 mcg/day is recommended

• Folic Acid: 4 mg/day prior to and during pregnancy

• Other possible deficiencies: Vitamin A, Vitamin K, zinc

MALE OBESITY

Mechanism

Andrology 2014; 2: 809

Male Obesity and Fertility

• Endocrine abnormalities• Reduced SHBG• Reduced testosterone

levels• Increased estrogen

levels• Insulin resistance

• Reduced spermatogenesis• Reduced sperm quality • Impaired sperm motility

• Erectile dysfunction

• Decreased libido

Male obesity and ART• Obese men and normal BMI women have increased time

to conception compared with normal weight couples.

• Increase pregnancy loss has been attributed to reduced blastocyst development, sperm binding and fertilization rates during IVF.

Andrology 2014; 2:809

Weight loss and male fertility• Literature is limited in this area.

• Weight loss has been associated with increases in testosterone levels, SHBG, and anti-mullerian hormone.

• Some studies have shown improvement in sperm count

Bariatric Surgery and Male Fertility• Literature is limited.

A small retrospective cohort study (2009)• Morbidly obese men:• 22 post Roux-en-Y gastric bypass vs 42 controls

• Decreased serum estradiol• Increased total and free testosterone

• This hasn’t been consistently demonstrated.

• A case series reported negative impact of bariatric surgery on spermatogenesis despite normal sex hormones.

• Authors suggested nutritional deficiencies may contribute. Andrology 2014; 2: 809

Summary• Obesity impacts both female and male fertility and not limited

to endocrine disorders

• ART outcomes maybe influenced by both female and male obesity.

• Pre-conception counselling should include discussion on the risks of obesity and focus on promoting physical activity and healthy dietary choices.

• More prospective research is needed to evaluate the risks and benefits of bariatric surgery with respect to fertility and ART outcomes.

Obstetrical Risks and Obesity

Obstetrical risks and obesity• Infertility• Failure of contraception• Gestational or type 2 diabetes

• Preeclampsia• Risk of c-section• Surgical complications

• Wound• Respiratory• thrombosis

• First trimester loss• Late pregnancy loss• Macrosomia• Congenital anomalies

• Neural tube• Cardiac• More difficult to diagnose

• Decreased breast feeding

For every 1 increase in BMI (kg/m2),the risk of a neural tube defect

increases 7%

Watkins, Pediatrics 2003

Prepregnancy counselling• Many women don’t plan their pregnancies• a negative pregnancy test is a good opportunity to reinforce importance of planning

• Women who are least likely to plan• Smokers• Single• Lower socioeconomic• Poor relationship with HCP• Perceive HCP as discouraging

+ve pregnancy test MD appt

Increased risk of congenital anomalies in overweight/obese• Many studies support increased risk

• Population based case-control, Metropolitan Atlanta Congenital Defects program

• Overweight (BMI 25.0-29.9)• Cardiac 2.0 (1.2-3.1)• Multiple anomalies 1.9 (1.1-3.4)

• Obese (BMI ≥ 30)• Spina bifida OR 3.5 (1.2-10.3)• Omphalocele 3.3 (1.0-10.3)• Cardiac 2.0 (1.2-3.4)• Multiple anomalies 2.0 (1.0-3.8)

Watkins et al., Pediatrics 2003

Why are offspring of obese women more likely to have a congenital anomaly?

• Folic acid• Glucose• Medications• ?other

Will more folate help obese women?

• Folate levels have decreased 16% since fortification of cereal (NHANES data)

• MMWR weekly Jan 5, 2007

• NTD increased 1.2 fold per 10 kg maternal weight even after fortification

• Ray, Am J Obstet Gynecol 2005

• Obese women less likely to eat cereals, vegetables• Laraia, Public Health Nutr 2007

• Obese women have lower serum folate levels with same intake – need to take an additional 350 ug/day

• Mojtabai, Eur J Epidemiol 2004

Glucose is a teratogen

• Sacral agenesis

ACE inhibitor exposure in pregnancy

Bowen, Am J Obstet Gynecol 2008

Case• Ten months later, Lucy is now 14 weeks pregnant. She has gained 7.7 kg (17 lb). She is attending her first antenatal care visit.

• What possible pregnancy complications is Lucy at higher risk for?

• What recommendation do you make for her nutritional health and weight gain during this pregnancy?

Ottawa Citizen,

April 21, 2008

Obstetrical risks and obesity• Infertility• Failure of contraception• Gestational or type 2 diabetes• Preeclampsia• Risk of c-section• Surgical complications

• Wound• Respiratory• Thrombosis• anaesthesia

• First trimester loss• Late pregnancy loss• Macrosomia• Congenital anomalies

• Neural tube• Cardiac• More difficult to diagnose

• Decreased breast feeding• Longterm maternal and childhood

obesity

Gestational weight gain• Overweight and obese women are more likely to gain more than IOM recommendations

• GWG associated with poor obstetrical outcomes

• GWG associated with long term weight retention

• GWG associated with increased risk of child adiposity at 3 years (?important motivator)

Oken, Am J Obstet Gynecol 2007

Jensen, Diabetes Care 2005

Case• At 29 weeks gestation, the 2hOGTT is abnormally elevated.

She has now gained a total of 23.2 kg (51 lb).

• What is the maternal diagnosis?

• What treatment options should now be implemented?

• What additional counselling and management options would you recommend?

• At this point, identify potential pregnancy-related complications:

• a) maternal • b) foetal

Gestational Diabetes• Carbohydrate intolerance with onset or first recognition in pregnancy

• 2-4% of pregnancies

• Same risk factors as type 2 diabetes

• Recommended that all women screened at 24-28 weeks

Adverse Outcomes

Reasons to look for GDM

• index pregnancy• macrosomia• hypoglycemia in neonate• fetal loss

• offspring• type 2 dm• obesity

• maternal - type 2 dm

2013 CDA Diagnostic Criteria for GDM

PREFERRED APPROACH (2 steps)

1. 50 gram glucose challenge test

2. 75 gram oral glucose tolerance test

ALTERNATIVE APPROACH (1 step)

1. 75 gram oral glucose tolerance test

2013

2013 GDM Diagnosis: Two Approaches2013

Rates of Postpartum Type 2 Diabetes in Mothers with GDM

• Women with GDM have 20% risk of type 2 diabetes within 9 years compared to 2% in women without GDM

Feig, CMAJ July 29, 2008

Case:• At 37 weeks gestation, Lucy’s total weight gain is 30.9 kg (68 lb). An ultrasound reveals an estimated foetal weight of 3.8 kg (8 lb, 6 oz) and polyhydramnios. The foetal well-being score is 6/8.

• Identify any additional potential foetal and neonatal complications.

• At this point, what recommendations should be instituted in preparation for labour and delivery?

Obstetrical risks and obesity• Infertility• Failure of contraception• Gestational or type 2

diabetes• Preeclampsia• Risk of c-section• Surgical complications

• Wound• Respiratory• Thrombosis• anaesthesia

• First trimester loss• Late pregnancy loss• Macrosomia• Congenital anomalies

• Neural tube• Cardiac• More difficult to diagnose

• Decreased breast feeding• Longterm maternal and

childhood obesity

BMI is a risk factor for C-Section

Barau et al BJOG 2006

Uterine Contractility?

Zhang et al BJOG 2007

Figure 1. The skin to lumbar epidural space distance (STLESD) predicted by body mass index (calculated as weight in kilograms divided by the square of height in meters) for the Caucasian, African American (AA), Hispanic, Asian, and Indian/Pakistani/Bangladeshi/Sri Lankan (I/P/B/S) ethnic populations (model R2 = 0.423).

From: D’Alonzo et al. Reg Anesth Pain Med. 2008;33:24-9

LIMIT OF REG. EPIDURAL NEEDLE

• At 38.3 weeks gestation, Lucy undergoes a caesarean section for failure to progress

• What potential immediate and delayed medical and surgical post-delivery complications can you anticipate for Lucy?

• Suggest appropriate postpartum care for Lucy.

• Identify potential neonatal complications and strategies for care.

Obstetrical risks and obesity• Infertility• Failure of contraception• Gestational or type 2

diabetes• Preeclampsia• Risk of c-section• Surgical complications

• Wound• Respiratory• Thrombosis• anaesthesia

• First trimester loss• Late pregnancy loss• Macrosomia• Congenital anomalies

• Neural tube• Cardiac• More difficult to diagnose

• Decreased breast feeding• Longterm maternal and

childhood obesity

Breastfeeding

• Rates are reduced in obese and T2DM woman

• Difficulties with infant latching• Delayed arrival of milk• Increased obstetrical complications including operative delivery

• Body image discomfort • Desire to start oral hypoglycemic and other drugs

Intention to Breastfeed

BMI < 25

BMI >25

BMI>30

2007-2008

94% 91% 89%

2008-2009

92% 90% 89%

Source: BORN Ontario (Niday Perinatal Database)

Exclusive Breastfeeding on d/c

BMI < 25

BMI > 25

BMI>30

2007-2008

65% (94%)

53%(91%)

45%(89%)

2008-2009

64%(92%)

53%(90%)

45%(89%)

Source: BORN Ontario (Niday Perinatal Database)

Breastfeeding associated with better maternal and offspring outcomes

• May reduce offspring obesity and risk of type 2 diabetes

• Lactation may attenuate unfavourable metabolic risk factors, promote pp weight loss• Gunderson Obstet Gynecol 2007

Need to target this group for breastfeeding support

The next generation

• Increased risk of obesity, diabetes, metabolic syndrome• Risk of obesity if maternal

BMI>30 in first trimester• 2 yrs 15%• 3 yrs 21%• 4 yrs 24%

Whitaker, Pediatrics 2004

Potential interventions

• Prepregnancy• Optimization of glucose, BP• Discontinue medications not

indicated in pregnancy• Adequate folic acid• Weight loss

• Consider bariatric surgery

• Intrapartum• Limit gestational weight gain• Prevent pre-eclampsia

• Postpartum• Improve breast feeding rates• Reduce weight retention• Enhance screening• Prevention strategies for CV

disease and diabetes

Thank you