Obesity(overweight) and female fertility

Doctors describe overweight and obesity as excessive fat accumulation that may impair health.

To distinguish between both concepts in adults is used body mass index (BMI). It is marked as a person’s weight in kilograms divided by the square of his height in meters (kg/m2).

For adult women, overweight and obesity are defined as follows[1]:

  • overweight is a BMI ≥ 25
  • obesity is a BMI ≥ 30

Excessive fat deposition is associated with a variety of female fertility issues.

Polycystic ovary syndrome (PCOS)

In women, extra adipose tissue provokes polycystic ovary syndrome (PCOS)[2], a highly prevalent endocrine female disorder[3].

PCOS is a group of symptoms that attacks the ovaries, which produce estrogen and progesterone — hormones that manage the menstrual cycle. The ovaries also release a small number of androgens (male hormones). Three main features of PCOS are:

  • cyst growth in the ovaries
  • increased male hormones
  • menstrual irregularity

In PCOS, many tiny, fluid-filled cysts grow inside the ovaries. These cysts are follicles, each containing an immature egg that never develops ultimately to trigger ovulation. The reduction of ovulation modifies estrogen, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels while increasing androgen levels.

Extra male hormones disrupt the menstrual cycle, leading to fewer periods than usual.  Testosterone and other androgens above the norm can harm a womanʼs fertility.

Obese women with polycystic ovary morphology (PCOM) had a higher chance of developing PCOS than nonobese women with PCOM[4].  Studies report that approximately 76% of women with PCOS have obesity.

Anovulation

Excessive weight is usually connected with ovulatory dysfunction[5]. 

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH), produced in the pituitary gland, regulate ovulation. FSH stimulates the ovary to release a follicle that contains an egg, and then LH triggers the ovary to free a mature egg. 

The mechanism of anovulation in obesity remains unclear. Insulin resistance is enhanced in obese women. It is proved that insulin stimulates estrogen production, causing inappropriate estrogen levels in the developing follicle[6]. By augmenting LH effects, insulin suppresses the final differentiation of follicle cells[7]. Thus, premature luteinization and follicular arrest lead to menstrual cycle disturbances and obesity-related anovulation. 

Even with regular menstrual cycles, obese women show diminished LH  amplitude, sometimes followed by prolonged folliculogenesis and decreased luteal progesterone levels. Thus, the ovulation process is disturbed.

In addition, increased adipokines, especially leptin, generated in adipose tissue can directly inhibit ovarian function[8].

Decreased oocyte quality

Obesity alters oocyte morphology[9]. Blastocysts developed from oocytes of obese women are minor, include fewer cells, with higher triglyceride content, lower glucose consumption, and changed amino acid metabolism compared with embryos from normal-weight women (BMI <24.9 kg/m2)10.

Moreover, obesity causes follicle apoptosis, oxidative stress in oocyte complexes, oocytes division defects, poor embryo development with reduced survival, and abnormal growth[11].

Infertility treatment outcome

Excessive fat accumulation causes destroying of embryo quality during in vitro fertilization (IVF) in women younger than 35 years old[12]. Some studies proved that obesity reduces fertilization[13]. Women with a BMI >25 kg/m2 have smaller oocytes that are less likely to complete post-fertilization.

Obese women undergoing IVF also have a weakened chance of clinical pregnancy compared with normal-weight women. A systematic review represents that overweight women have a 10% lower live birth rate than women of average weight during IVF[14]. According to recent studies, obesity reduces embryo implantation.

Obesity is associated with higher doses of medications to influence ovulation or stimulate ovaries for IVF. When hormones gonadotropins are used for ovulation induction, overweight correlates with an increased quantity of administered FSH, fewer mature follicles, and a decreased chance of ovulation[15].

Pregnancy complications

During pregnancy, obese women have an enormously higher risk of complications, including preeclampsia, gestational diabetes, preterm delivery, and miscarriage[16].

Preeclampsia is defined as a condition caused by high blood pressure and significant amounts of protein in the urine. Preeclampsia also increases the chance of cesarean section. 

When a woman faces gestational diabetes, the chances of a baby’s overweight are increased. 

The connection between obesity and miscarriage has been found in both natural and assisted fertilization. Suggested mechanisms are endometrial damages, alterations in embryo quality, and uterine receptivity[17].

Studies confirm the associations between maternal obesity and congenital anomalies such as neural tube defects, cardiovascular abnormalities, cleft lip and palate, hydrocephalus, etc.[18].

As a result, the obesity epidemic redounds to increasing fertility difficulties, negatively impacting womenʼs and their offspring’s health.

References

  1. World Health Organization 
  2. Dağ ZÖ, Dilbaz B. Impact of obesity on infertility in women. J Turk Ger Gynecol Assoc. 2015 Jun 1;16(2):111-7. doi: 10.5152/jtgga.2015.15232. PMID: 26097395; PMCID: PMC4456969. 
  3. Fauser BC, Tarlatzis BC, Rebar RW, Legro RS, Balen AH, Lobo R, Carmina E, Chang J, Yildiz BO, Laven JS, Boivin J, Petraglia F, Wijeyeratne CN, Norman RJ, Dunaif A, Franks S, Wild RA, Dumesic D, Barnhart K. Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril. 2012 Jan;97(1):28-38.e25. doi: 10.1016/j.fertnstert.2011.09.024.
  4. Liou TH, Yang JH, Hsieh CH, Lee CY, Hsu CS, Hsu MI. Clinical and biochemical presentations of polycystic ovary syndrome among obese and nonobese women. Fertil Steril. 2009 Dec;92(6):1960-5. doi: 10.1016/j.fertnstert.2008.09.003.
  5. Janet W. Rich-Edwards, Marlene B. Goldman, Walter C. Willett, David J. Hunter, Meir J. Stampfer, Graham A. Colditz, JoAnn E. Manson. Adolescent body mass index and infertility caused by ovulatory disorder. American Journal of Obstetrics and Gynecology. 1994. 171-177. doi: 10.1016/0002-9378(94)90465-0.
  6. Willis D, Mason H, Gilling-Smith C, Franks S. Modulation by insulin of follicle-stimulating hormone and luteinizing hormone actions in human granulosa cells of normal and polycystic ovaries. J Clin Endocrinol Metab. 1996 Jan;81(1):302-9. doi: 10.1210/jcem.81.1.8550768.
  7. Hillier SG. Current concepts of the roles of follicle stimulating hormone and luteinizing hormone in folliculogenesis. Hum Reprod. 1994 Feb;9(2):188-91. doi: 10.1093/oxfordjournals.humrep.a138480.
  8. Agarwal SK, Vogel K, Weitsman SR, Magoffin DA. Leptin antagonizes the insulin-like growth factor-I augmentation of steroidogenesis in granulosa and theca cells of the human ovary. J Clin Endocrinol Metab. 1999 Mar;84(3):1072-6. doi: 10.1210/jcem.84.3.5543.
  9. Raffaella Depalo,Gabriella Garruti,Ilaria Totaro,Mariantonietta Panzarino,Margherita Patrizia Vacca,Francesco Giorgino &Luigi Eustacchio Selvaggi. Oocyte morphological abnormalities in overweight women undergoing in vitro fertilization cycles. Gynecological Endocrinology. Apr 2011. 880-884 . doi: 10.3109/09513590.2011.569600
  10.  Christine Leary, Henry J. Leese, Roger G. Sturmey. Human embryos from overweight and obese women display phenotypic and metabolic abnormalities. Human Reproduction. Volume 30, Issue 1, January 2015. Pages 122–132. doi: 10.1093/humrep/deu276
  11.  Wu LL, Dunning KR, Yang X, Russell DL, Lane M, Norman RJ, Robker RL. High-fat diet causes lipotoxicity responses in cumulus-oocyte complexes and decreased fertilization rates. Endocrinology. 2010 Nov;151(11):5438-45. doi: 10.1210/en.2010-0551. 
  12.  M Metwally, R Cutting, A Tipton, J Skull, WL Ledger, TC Li. Effect of increased body mass index on oocyte and embryo quality in IVF patients. Reproductive BioMedicine Online. Volume 15, Issue 5, 2007, Pages 532-538, ISSN 1472-6483. doi: 10.1016/S1472-6483(10)60385-9.
  13.  Raoul Orvieto, Simion Meltcer, Ravit Nahum, Jacob Rabinson, Eyal Y. Anteby, Jacob Ashkenazi. The influence of body mass index on in vitro fertilization outcome. International Journal of Gynecology & Obstetrics. Volume 104, Issue 1, 2009, Pages 53-55, ISSN 0020-7292. doi: 10.1016/j.ijgo.2008.08.012.
  14.  A.M.H. Koning, M.A.Q. Mutsaerts, W.K.H. Kuchenbecher, F.J. Broekmans, J.A. Land, B.W. Mol, A. Hoek. Complications and outcome of assisted reproduction technologies in overweight and obese women. Human Reproduction. Volume 27, Issue 2, February 2012, Pages 457–467. doi: 10.1093/humrep/der416.
  15.  Irene Souter, Lina M. Baltagi, Damien Kuleta, John D. Meeker, John C. Petrozza. Women, weight, and fertility: The effect of body mass index on the outcome of superovulation/intrauterine insemination cycles. Fertility and Sterility. Volume 95, Issue 3, 2011, Pages 1042-1047, ISSN 0015-0282. doi: 10.1016/j.fertnstert.2010.11.062.
  16.   Joshua L Weiss, Fergal D Malone, Danielle Emig, Robert H Ball, David A Nyberg, Christine H Comstock, George Saade, Keith Eddleman, Suzanne M Carter, Sabrina D Craigo, Stephen R Carr, Mary E D’Alton. Obesity, obstetric complications and cesarean delivery rate–a population-based screening study. American Journal of Obstetrics and Gynecology. Volume 190, Issue 4, 2004, Pages 1091-1097, ISSN 0002-9378. doi: 10.1016/j.ajog.2003.09.058.
  17.  Luke B, Brown MB, Stern JE, Missmer SA, Fujimoto VY, Leach R; SART Writing Group. Female obesity adversely affects assisted reproductive technology (ART) pregnancy and live birth rates. Hum Reprod. 2011 Jan;26(1):245-52. doi: 10.1093/humrep/deq306.
  18. Stothard KJ, Tennant PWG, Bell R, Rankin J. Maternal Overweight and Obesity and the Risk of Congenital Anomalies: A Systematic Review and Meta-analysis. JAMA.2009;301(6):636–650. doi:10.1001/jama.2009.113.