aPreconception Care in Obese WomenLisa Webber MA BMBCh PhD MRCOGConsultant GynaecologistSpecialist in Reproductive Medicine
Principles of preconception careTo address:• undiagnosed, untreatedor poorly controlledmedical conditions• immunization hi...
Principles of preconception careTo address:• undiagnosed, untreatedor poorly controlledmedical conditions• immunization hi...
Preconception care for obese women• Weight reduction– identification & treatment of eating disorders– consider bariatric s...
(Average height woman 1.63m tall)startingBMItargetBMItargetweightloss (%)targetweightloss (kg)35 30 14.7% 13 kg40 35 12.5%...
Optimisation of weight - impact of timeMarital fertility rates [Drawn from Menken et al. (1986) Science]
Reproductive effects of obesity
Reproductive effects of obesityImpact of obesity on–fertility–the pregnant mother–the fetus–the child
Impact of obesity on fertility• Spontaneous conception rate probablyreduced in ovulatory women
Impact of obesity on fertilityconception70503010cumulativepregnancyrateafter12cyclesDI(%)<20 20.1-25 25.1-30 >30BMI kg/m2Z...
Impact of obesity on fertilityconception70503010<0.7 0.7-0.75 0.76-0.8 0.81-0.85 >0.85waist:hip ratioZaadstra et al 1993cu...
Impact of obesity on fertility• Spontaneous conception rate probablyreduced in ovulatory women• Ovulation rate reduced in ...
Women with PCOS vs weight-matched controls• insulin resistant (Robinson et al 1993)–downstream to insulin receptor (Dunaif...
Obesity causes:• peripheral insulin resistance• resulting in hyperinsulinaemiaImpact of obesity on fertilityovulationPCOS ...
Impact of obesity on fertilityovulation• Insulin is a gonadotrophin• Stimulating effect on the ovary similar toluteinizing...
Impact of obesity on fertility• Spontaneous conception rate probablyreduced in ovulatory women• Ovulation rate reduced in ...
Impact of obesity on fertilityovulation induction: clomifene/FSH2040608018-24 30-34 >35BMI kg/m2ovulationrate(%) Al-Azemi ...
Impact of obesity on fertilityovulation induction: LOD20406080<29 29-34 >34BMI kg/m2ovulationrate(%) Amer et al 2004100pre...
• Clomifenehigher dose• Gonadotrophinsmore treatment dayshigher threshold dosehigher total dosehigher costBalen et al 2006...
• Higher risk of hyperstimulation• Ultrasonographic monitoring more difficultImpact of obesity on fertilityovulation induc...
Impact of obesity on fertility• Spontaneous conception rate probablyreduced in ovulatory women• Ovulation rate reduced in ...
Impact of obesity on fertilityall fertility treatments302010ongoingpregnancies(%)18-32 32-35 35-40 >40 p=0.002BMI kg/m2Gil...
• Oocyte quality?• Embryo quality?• Endometrium?• Environment?Impact of obesity on fertilityassisted reproduction
Impact of obesity on fertilityassisted reproductionBellver et al 20106500 ICSI cycles / 6.4% (419) BMI > 30 kg/m2= fertili...
• Higher doses of gonadotrophin forsuperovulation & controlled ovarianhyperstimulation• Higher costImpact of obesity on fe...
Impact of obesity on fertility• Spontaneous conception rate probablyreduced in ovulatory women• Ovulation rate reduced in ...
Impact of weight loss on reproductionEffectivenessIncreased ovulation & pregnancy rates in obeseanovulatory women with mod...
Impact of obesity on obstetrics
• gestational diabetes• gestational hypertension / pre-eclampsia• miscarriage• caesarean section• preterm delivery• macros...
Metwally et al 2008Meta-analysis of 16 eligible studies• Risk of miscarriage increased when BMI>25kg/m2 (OR 1.67, 95% CI 1...
CEMACH 2003-5:• 28% of mothers who died were obese• 16-19% of maternity population obeseImpact of obesity on the mothermat...
Impact of obesity on the offspring
• congenital anomaly• stillbirth• neonatal death• vertical transmissionImpact of obesity on the offspring
Increased risks for mother and childImpact of obesity on pregnancy
Stothard et al 2009Systematic review & meta-analysis: >30kg/m2• Neural tube defects• Cardiovascular anomalies• Cleft palat...
Obesity and neural tube defectsRasmussen et al 2008: meta-analysis of 12observational cohort studiesOdds ratio for NTD cf ...
Folic acid• Maternal folate deficiency associated with NTDs• Periconception folic acid reduces 1st occurrence& recurrenceL...
High dose folic acid:unproven in obesity• No evidence that supplementation reducesincidence of NTDs in the obeseRay et al ...
Vitamin D supplements• 25% of women 19-24yo & 17% of 25-34yo atrisk of vitamin D deficiency in BritainOffice for National ...
Summary• Most preconception care deliveredopportunistically• All healthcare practitioners should be awareof the reproducti...
Preconception care in the obese• Weight reduction: realistic goals, appreciationof time constraints• Counsel on reproducti...
lisa.webber@uclh.nhs.uk
Webber Teoh o&p2013
Webber Teoh o&p2013
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  1. 1. aPreconception Care in Obese WomenLisa Webber MA BMBCh PhD MRCOGConsultant GynaecologistSpecialist in Reproductive Medicine
  2. 2. Principles of preconception careTo address:• undiagnosed, untreatedor poorly controlledmedical conditions• immunization history• nutritional issues• family history & geneticrisk• substance use/high riskbehaviours• occupational/environmental exposures• social issues• mental health issues
  3. 3. Principles of preconception careTo address:• undiagnosed, untreatedor poorly controlledmedical conditions• immunization history• nutritional issues• family history & geneticrisk• substance use/high riskbehaviours• occupational/environmental exposures• social issues• mental health issuesfor obese women✓✓✓ ✓✓
  4. 4. Preconception care for obese women• Weight reduction– identification & treatment of eating disorders– consider bariatric surgery if BMI >35• Information about risks of obesity in pregnancy& childbirth• Nutritional supplements?• Diabetes screening?
  5. 5. (Average height woman 1.63m tall)startingBMItargetBMItargetweightloss (%)targetweightloss (kg)35 30 14.7% 13 kg40 35 12.5% 13 kg40 30 25.4% 27 kgWeight reduction
  6. 6. Optimisation of weight - impact of timeMarital fertility rates [Drawn from Menken et al. (1986) Science]
  7. 7. Reproductive effects of obesity
  8. 8. Reproductive effects of obesityImpact of obesity on–fertility–the pregnant mother–the fetus–the child
  9. 9. Impact of obesity on fertility• Spontaneous conception rate probablyreduced in ovulatory women
  10. 10. Impact of obesity on fertilityconception70503010cumulativepregnancyrateafter12cyclesDI(%)<20 20.1-25 25.1-30 >30BMI kg/m2Zaadstra et al 1993
  11. 11. Impact of obesity on fertilityconception70503010<0.7 0.7-0.75 0.76-0.8 0.81-0.85 >0.85waist:hip ratioZaadstra et al 1993cumulativepregnancyrateafter12cyclesDI(%)
  12. 12. Impact of obesity on fertility• Spontaneous conception rate probablyreduced in ovulatory women• Ovulation rate reduced in women with PCOS
  13. 13. Women with PCOS vs weight-matched controls• insulin resistant (Robinson et al 1993)–downstream to insulin receptor (Dunaif et al 1995)• hyperinsulinaemic–increased secretion from β cells (Holte et al 1994)contributes to obesityImpact of obesity on fertilityovulation
  14. 14. Obesity causes:• peripheral insulin resistance• resulting in hyperinsulinaemiaImpact of obesity on fertilityovulationPCOS and obesity have synergistic detrimentaleffects on insulin metabolism
  15. 15. Impact of obesity on fertilityovulation• Insulin is a gonadotrophin• Stimulating effect on the ovary similar toluteinizing hormone (LH)• Insulin potentiates effect of LH: even in IR• Follicles in PCO respond prematurely to LH &insulin which leads to follicle arrest• So high LH or high insulin = less frequentovulation
  16. 16. Impact of obesity on fertility• Spontaneous conception rate probablyreduced in ovulatory women• Ovulation rate reduced in women with PCOS• Ovulation induction is less successful
  17. 17. Impact of obesity on fertilityovulation induction: clomifene/FSH2040608018-24 30-34 >35BMI kg/m2ovulationrate(%) Al-Azemi et al 2004
  18. 18. Impact of obesity on fertilityovulation induction: LOD20406080<29 29-34 >34BMI kg/m2ovulationrate(%) Amer et al 2004100pregnancyrate(%)
  19. 19. • Clomifenehigher dose• Gonadotrophinsmore treatment dayshigher threshold dosehigher total dosehigher costBalen et al 2006Impact of obesity on fertilityovulation induction
  20. 20. • Higher risk of hyperstimulation• Ultrasonographic monitoring more difficultImpact of obesity on fertilityovulation induction
  21. 21. Impact of obesity on fertility• Spontaneous conception rate probablyreduced in ovulatory women• Ovulation rate reduced in women with PCOS• Ovulation induction is less successful• ART outcomes compromised
  22. 22. Impact of obesity on fertilityall fertility treatments302010ongoingpregnancies(%)18-32 32-35 35-40 >40 p=0.002BMI kg/m2Gillett et al 2006
  23. 23. • Oocyte quality?• Embryo quality?• Endometrium?• Environment?Impact of obesity on fertilityassisted reproduction
  24. 24. Impact of obesity on fertilityassisted reproductionBellver et al 20106500 ICSI cycles / 6.4% (419) BMI > 30 kg/m2= fertilization rate= embryo quality (day of ET, no of embryos,blastocyst transfers, embryo Q on D2/3) implantation pregnancy live birth
  25. 25. • Higher doses of gonadotrophin forsuperovulation & controlled ovarianhyperstimulation• Higher costImpact of obesity on fertilityassisted reproduction
  26. 26. Impact of obesity on fertility• Spontaneous conception rate probablyreduced in ovulatory women• Ovulation rate reduced in women with PCOS• Ovulation induction is less successful• ART outcomes compromisedProbability of pregnancy, spontaneous &assisted, is reduced
  27. 27. Impact of weight loss on reproductionEffectivenessIncreased ovulation & pregnancy rates in obeseanovulatory women with modest weight loss• >5% weight loss Kiddy et al 1992• average weight loss 6.3kg Clark et al 1995• improvement in insulin sensitivity & central fatHuber-Buchholz et al 1999
  28. 28. Impact of obesity on obstetrics
  29. 29. • gestational diabetes• gestational hypertension / pre-eclampsia• miscarriage• caesarean section• preterm delivery• macrosomia• urinary tract & wound infections• thromoboembolismImpact of obesity on mother & baby
  30. 30. Metwally et al 2008Meta-analysis of 16 eligible studies• Risk of miscarriage increased when BMI>25kg/m2 (OR 1.67, 95% CI 1.25-2.25)Lashen et al 2004• Risk of recurrent miscarriage increased whenBMI >30kg/m2 (OR 3.5, 95% CI 1.03-12.01)Impact of obesity on miscarriage
  31. 31. CEMACH 2003-5:• 28% of mothers who died were obese• 16-19% of maternity population obeseImpact of obesity on the mothermaternal mortality
  32. 32. Impact of obesity on the offspring
  33. 33. • congenital anomaly• stillbirth• neonatal death• vertical transmissionImpact of obesity on the offspring
  34. 34. Increased risks for mother and childImpact of obesity on pregnancy
  35. 35. Stothard et al 2009Systematic review & meta-analysis: >30kg/m2• Neural tube defects• Cardiovascular anomalies• Cleft palate +/- cleft lip• Anorectal atresia• Hydrocephaly• Limb reduction anomaliesImpact of obesity on congenital anomality
  36. 36. Obesity and neural tube defectsRasmussen et al 2008: meta-analysis of 12observational cohort studiesOdds ratio for NTD cf healthy weight• overweight: OR 1.22 (95% CI 0.99-1.49)• obese: OR 1.7 (95% CI 1.34-2.15)• severely obese OR 3.11 (95% CI 1.75-5.46)
  37. 37. Folic acid• Maternal folate deficiency associated with NTDs• Periconception folic acid reduces 1st occurrence& recurrenceLumley et al Cochrane Database of systematic reviews 2001 (3)• Risk in women with previous NTD pregnancyreduced by 4mg/dayMRC Vitamin Study Research Group Lancet 1991 CMACE• CEMACE/RCOG – periconception high dose folicacid (5mg) for BMI >30
  38. 38. High dose folic acid:unproven in obesity• No evidence that supplementation reducesincidence of NTDs in the obeseRay et al 2005• Red cell folate not significantly lower in obesepregnant women, despite lower folate intake cfnormal weightMojtabai 2004• Possible role for periconception hyperglycaemia- High dose folate not part of ACOG preconceptionrecommendations for the obese
  39. 39. Vitamin D supplements• 25% of women 19-24yo & 17% of 25-34yo atrisk of vitamin D deficiency in BritainOffice for National Statistics 2004• Prepregnancy BMI >30 associated withmaternal vitamin D deficiency & low cordblood levels• Bodanar et al 2007• Encourage obese pregnant women to takesupplements: 10mcg daily
  40. 40. Summary• Most preconception care deliveredopportunistically• All healthcare practitioners should be awareof the reproductive risks of obesity and beprepared to counsel women (or arrangereferral)• Inter-pregnancy may be an opportune timedue to increased contact with healthcarepractitioners
  41. 41. Preconception care in the obese• Weight reduction: realistic goals, appreciationof time constraints• Counsel on reproductive risks• Supplements – folic acid, vitamin D• Screen for diabetes when appropriate– family history– anovulatory PCOS• Engage with obese women to ensure theyaccess appropriate care
  42. 42. lisa.webber@uclh.nhs.uk

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