1. Obesity is associated with female and male infertility through multiple mechanisms that impact the hypothalamic-pituitary-gonadal axis, gamete quality, embryo development, implantation, and pregnancy outcomes. 2. For females, obesity is linked to irregular menstrual cycles, ovulation disorders, polycystic ovary syndrome, and impaired endometrial receptivity. It can decrease fertility, increase miscarriage risk, and lead to poorer outcomes with assisted reproduction. 3. For males, obesity is associated with decreased testosterone and sperm quality, as well as erectile dysfunction. Weight loss through lifestyle changes and bariatric surgery can help address obesity-related infertility issues.

1. dr. MohamedAlajami

2. dr. MohamedAlajami
Higher Studies in Obs.Gyne- MD
Lecturer in HAMA University
Obesity and infertility

3. INTRODUCTION
dr. M. Alajami
֎Obesity ~ Latin obesus, ‘‘one who has become plump through
eating.’’ ( ‫هو‬
‫األكل‬ ‫من‬ ‫الجسم‬ ‫ممتلئ‬ ‫أصبح‬ ‫الذي‬ )
֎ It may have first appeared in the writings of Thomas Venner in 1620
֎ However, the negative effect of obesity on an individual’s health has been known
for a longer time and can be found in the writings of Hippocrates, Galen, and
Avicenna.
Lancet 2005;365:1843.
Lancet 2005;366:204.

4. dr. M. Alajami
֎ Avicenna was the first who described the relationship between obesity and male
infertility in his encyclopedic medical book The Canon of Medicine.
֎ In modern times: the relationship between obesity infertility has been largely
ignored until recently.
֎ Interest in the rapid increase in obesity has brought to light the detrimental
effects of obesity on health in general and on the reproductive function in
particular. Lancet 2005;365:1843.
JAMA 2004;291:2847–50.
INTRODUCTION

5. dr. M. Alajami
֎ Obesity is an accumulation of excess body fat that has a detrimental impact on
health outcomes.
 closely associated with insulin resistance
֎ WHO 2000 definition based on the body mass index (BMI) (kg/m2)
 Obesity class I = BMI of >30 kg/m2
 Obesity class II (Morbid) = BMI of >35 kg/m2
 Obesity class III (Morbid) = BMI > 40 kg/m2
Clinical characterization of obesity
(Okorodudu et al., 2010).
Hum Reprod Update 2003;9:359–72.

6. dr. M. Alajami
Clinical characterization of obesity

7. dr. M. Alajami
Type and distribution of body fat accumulation are of clinical importance.
֎ Complications of obesity rise exponentially with visceral adiposity.
 Negative impact on human reproduction
֎ Waist circumference most closely reflects visceral adiposity.
(Alberti et al., 2009)
Clinical characterization of obesity
(Adler, Cassidy, Fricke, & Bonduriansky, 2013)
Waist circumference
 Normal men < 94 cm
 Normal women < 80 cm

8. dr. M. Alajami
֎ Complications of obesity mediated through complex and poorly understood
mechanisms:
1. Hyperinsulinemia (insulin resistance )
2. Hyperleptinemia
3. Inflammation (chronic systemic low-grade )
4. Oxidative stress
Clinical characterization of obesity

9. dr. M. Alajami
֎ Adipose tissues is a source of
1. hormones
2. Adipokines (as adiponectin, ghrelin, leptin, orexin, obestatin,….)
3. Pro-inflammatory cytokines
4. Endogenous and exogenous toxins.
(Leisegang & Henkel, 2018)
Functional properties of adipocytes

10. dr. M. Alajami
Functional properties of adipocytes

11. dr. M. Alajami
֎ Obesity is a global health problem has reached epidemic proportions
֎ Worldwide obesity has nearly tripled between 1975 and 2016
֎ all evidences suggest that the situation is likely to get worse ahead.
֎ expected to increase to > 40% of the global population by 2030
Epidemiology of obesity
(Davidson, Millar, Jones, Fatum, & Coward, 2015)
WHO 2020

12. dr. M. Alajami
 ~ 13% of the world’s adult population (> 650 million) were obese.
 11% of men
 15% of women
 39% of adults (> 1.9 billion) were overweight.
 39% of men
 40% of women.
 > 340 million children and adolescents aged 5-19 were overweight or obese
 38 million children < age of 5 were overweight or obese in 2019.
Epidemiology of obesity 2016
WHO 2020

13.  Most of the world's population live in countries where overweight and obesity
kills more people than underweight.
dr. M. Alajami
Obesity Epidemiology
WHO 2020

14. Overweight and obese 2016
dr. M. Alajami

15. Middle East and North Africa 2016
dr. M. Alajami
Syria: 53.3%
Global position # 92

16. dr. M. Alajami
Mean BMI in Syrian women, 1975 to 2016
29.48 kg/m2

17. dr. M. Alajami
27.56 kg/m2
Mean BMI in Syrian men, 1975 to 2016

18. dr. M. Alajami
I. Nonmodifiable risk factors
1. Polygenetic predisposition
2. Epigenetic inheritance
3. Ageing (mediated predominantly through oxidative stress)
4. Female gender.
II. Poor socio-economic status
III. Psychological factors
IV. Reduced quantity or quality of sleep.
(Haslam & James, 2005)
Risk factors of obesity
(Leisegang, Henkel, & Agarwal, 2017)

19. dr. M. Alajami
VI. Poor nutritional options (increased energy-dense foods)
VII. Sedentary lifestyle.
 predominantly in ‘Westernized’ regions
 obesity is closely pandemic
(Haslam & James, 2005)
Risk factors of obesity
(Castro, Macedo-de la Concha, & Pantoja-Meléndez, 2017)
The most significant risk factor for obesity

20. dr. M. Alajami
VIII. Numerous medications are associated with obesity risk:
1. Thiazide diuretics and beta-blockers (hypertension)
2. Thiazolidinedione agents and insulin (type 2 diabetes mellitus)
3. Tricyclic and monoamine oxidase inhibitors (antidepressants)
4. Anti-psychotics
5. Oral contraceptive pills
6. Glucocorticoids
Risk factors of obesity
(Wofford, King, & Harrell, 2006)

21. dr. M. Alajami
Risk factors of obesity
 Obesity is preventable
WHO 2020

22. dr. M. Alajami
Obesity and infertility

23. INFERTILITY
dr. M. Alajami
֎Infertility is the lack of pregnancy despite regular unprotected sexual
intercourse after a year in women less than 35 years of age and after 6 months
in women 35 years and older. Fertili Steril 2013; 99: 63.

24. dr. M. Alajami
Female obesity and fertility

25. Female obesity and fertility
dr. M. Alajami
Fertility issues arising from obesity in females may include:
1. Incidences of Irregular menstrual cycles
2. Problems with ovulation
3. Increase time to pregnancy
4. Increased androgen levels
5. Polycystic ovarian syndrome (PCOS)
6. Increased risk of miscarriage
7. Risk of major pregnancy and delivery morbidities

26. dr. M. Alajami
֎ Obesity has a negative effect on reproductive potential.
֎ Obese women have increased time to pregnancy.
 even in the absence of ovulatory dysfunction.
֎ Reduced fecundity in eumenorrheic obese women
 a decline in fecundability ratios with increasing (BMI).
֎ Spontaneous conception declined linearly with each BMI point >29 kg/m2.
Hum Reprod 2010;25:253–64.
Hum Reprod 2007;22:1634–7.
Hum Reprod 2007;22:414–20.
Hum Reprod 2008;23:324–8.
Effects of obesity on female infertility

27. dr. M. Alajami
I. HPO AXIS
II. OOCYTE
III. EMBRYO
IV. ENDOMETRIUM
V. TRANSGENERATIONAL effects
Effects of obesity on female infertility

28. Mechanisms linking obesity with infertility
dr. M. Alajami
1
2
3

29. Effects on the female HPO AXIS
dr. M. Alajami
֎ Obesity affects regulation of the HPO axis.
֎ Obese women often have higher circulating levels of insulin, which is a
stimulus for increased ovarian androgen production.
֎ These androgens are aromatized to estrogen at high rates in the periphery
owing to excess adipose tissue, leading to negative feedback on the HPO axis
and affecting gonadotropin production.
Mol Cell Endocrinol 2010;316:172–9.
. Am J Obstet
Gynecol 2010;203:525–30.

30. dr. M. Alajami
֎ Central players
1. Insulin resistance
2. Hyperandrogenism
3. Elevated leptin
4. Leptin resistance
 the amplitude of LH pulsatility decreased significantly in eumenorrheic obese women,
pointing to a central defect that may be unique to this disease
GONADOTROPINS
Effects on the female HPO AXIS

31. Increased
1. insulin resistance
2. hyperinsulinemia
3. androgen levels
4. oligo/anovulation
5. cycle cancellation
6. risk of miscarriage
dr. M. Alajami
Effects of obesity upon PCOS
PCOS: A Leading Cause of Infertility
Reduced
1. SHBG
2. menstrual cyclicity
3. ovulation rates
4. response to gonadotrophin during
superovulation
5. success ART

32. EFFECTS ON THE OOCYTE
dr. M. Alajami
1. Early follicle atresia
2. Delayed meiotic maturation
3. Increased aneuploidy
4. Increased follicular apoptosis

33. EFFECTS ON THE OOCYTE
dr. M. Alajami
֎ Mechanism for oocyte organelle damage in obesity is lipotoxicity.
֎ higher levels of circulating free fatty acids (FFA) damage non adipose cells by
increasing reactive oxygen species (ROS) that induce mitochondrial and ER
stress leading to apoptosis.
֎ elevated levels of FFA in the follicular fluid correlated with abnormal morphology of
cumulus-oocyte complexes.
Semin Reprod Med 2016;34:5–10.
Fertil Steril 2011;95:1970–4.
lipotoxicity ROS apoptosis

34. EFFECTS ON THE EMBRYO
dr. M. Alajami
֎ Obese women are more likely to create poor quality embryos.
 less likely to develop after fertilization, and those that did reached the morula
stage more quickly.
֎ Embryos may also be susceptible to lipotoxicity
֎ Elevated leptin levels have a direct negative effect on the developing
embryo.
Reprod Biomed Online 2001;3:109–11.
Reprod Biomed Online 2007;15:532–8.

35. EFFECT ON THE ENDOMETRIUM
dr. M. Alajami
֎ Conflicting data:
 Obesity does not negatively affect endometrial receptivity.
 BMI is independent predictor of clinical pregnancy.
Fertil Steril 2005;83:1629–34.
Fertil Steril 2003;80:336–40.
Hum Reprod 2009;24:3082-9.
 Stromal Decidualization
 Endometrial Receptivity

36. dr. M. Alajami
֎ Endometrial decidualization is impaired in the obese women.
compromise endometrial receptivity and poor
implantation.
negatively affect the placentation process.
most pregnancy complications in obese.
Hum Reprod 2016;31:1315–26.
Decidualization
defects
Poor
implantation
Placental
dysfunction
Pregnancy
complications
EFFECT ON THE ENDOMETRIUM

37. TRANSGENERATIONAL EFFECTS
dr. M. Alajami
֎ Maternal obesity may confer a risk of metabolic dysfunction though multiple
generations.
֎ Children of obese mothers are more likely to develop obesity, type II diabetes,
and cardiovascular disease as adults.
֎ This may be due to epigenetic modifications in utero.

38. dr. M. Alajami
Management of obesity

39. Management of obesity
dr. M. Alajami
֎ 1st line of Management:
 Lifestyle changes like modification of diet , physical activity and daily habits

40. Management of obesity
dr. M. Alajami
֎ 1st line of Management
֎ 2nd line of Management: pharmacotherapy for
 BMI > 25 with comorbidities
 BMI > 27 without comorbidity
ᴥ Metformin: not a wt loss drug

41. Management of obesity
dr. M. Alajami
֎ 1st line of Management:
֎ 2nd line of Management: pharmacotherapy for
֎ Bariatric Surgery:
 Extreme obesity (BMI > 40) when diet and exercise fail

42. dr. M. Alajami
RX of female obesity infertility

43. dr. M. Alajami
Life –Style &
Nutrition Changes
• Diet
• Exercise
• Psychological
Counseling
ART
 IUI
 IVF
 ICSI
Surgical Intervention
 Bariatric Surgery
Pharmacological Intervention
 Appetite Suppressant, Weight Loss Drugs (Orlistat)
ᴥ Drugs Increase Suicidal Tendency
ᴥ Metformin: not a wt loss drug
1ST 2nd 3ed 4th
RX of female obesity infertility

44. dr. M. Alajami
 Bariatric surgery:
 the most effective therapy for severe obesity
 pregnancy is relatively contraindicated during the first 6–12 months after
surgery
 due to the inability of the reconstructed gastrointestinal tract to accommodate the
need for the increased nutrition that a developing pregnancy requires.
RX of female obesity infertility

45. dr. M. Alajami
 No clear dose-response relationship between weight loss in an obese patient
and fertility
RX of female obesity infertility
56%
48%
32%
25%
0%
10%
20%
30%
40%
50%
60%
Regular cycle Spontaneous
Ovulation
Spontaneous
pregnancy
live brith
‫المخطط‬ ‫عنوان‬

46. 1. Impaired USS image quality due to adipose tissue
2. Increased
 duration of stimulation
 total gonadotrophin dose required.
 follicular asynchrony
 cycle cancellation.
3. Poor response to superovulation
dr. M. Alajami
Effects of female obesity upon ART
Obesity leads to poorer prognosis with Assisted Reproduction

47. 4. Reduced
 follicular hCG concentration on day of ovum pickup (inverse correlation
with BMI).
 number of cumulus–oocyte complex at ovum pickup
 metaphase II oocytes pickup
 number of surplus good quality embryos available for cryopreservation
 pregnancy rates (halved for women with BMI > 35 kg/m2).
5. Increased miscarriage rates.
dr. M. Alajami
Effects of female obesity upon ART

48. Gonadotropin Resistance
dr. M. Alajami
1. Greater amount of body surface
2. Differences in absorption and metabolic clearance
3. Altered peripheral steroid metabolism
4. Impaired absorption due to increased subcutaneous fat

49. British Fertility Society guidelines
dr. M. Alajami
֎ Infertility treatment should be deferred until BMI <35 kg/m2
 preferably BMI <30 kg/m2 in young women with good ovarian reserve
© Unethical to refuse to accept a patient solely because she is obese
 Violation of Articles Human Rights
• 12 (Right to marry and found a family)
• 14 (Prohibition of discrimination).
NICE 2007
(ACOG, 2014)

50. Male infertility
dr. M. Alajami

51. Male infertility
dr. M. Alajami

52. dr. M. Alajami
I. Obesity and hormonal imbalances
1. Hypothalamic-pituitary-gonadal axis
2. Testicular steroidogenesis
3. Metabolic hormone imbalances
II. Obesity and spermatogenesis
III. Obesity and semen quality
IV. Obesity and sperm DNA integrity
V. Obesity and erectile dysfunction
Impact of Obesity on Male Reproduction

53. dr. M. Alajami
I. Obese men have decreased testosterone and gonadotropin levels, and
increased circulating estrogen levels.
 The increase estrogen is secondary to peripheral aromatization of androgens.
II. As estrogen negatively feedbacks onto the hypothalamus, a hypogonadotropic
hypogonad state is created leading to:
1. lower sperm counts
2. Increased rates of erectile dysfunction.
III. Increase in local heat impairs spermatogenesis.
֎ Ultimately sperm from obese men can contribute to poor embryo quality.
Fertil Steril. 2008;90(4):897–904
Hum Reprod Update. 2013;19(3):221–31.
Fertil Steril. 2008;90(5 Suppl):S21–9.
Reproduction. 2012;143(6):727–34.
2. poorer sperm quality
Impact of Obesity on Male Reproduction

54. dr. M. Alajami
֎ Obesity is adversely affect male infertility through
1. alteration in semen parameters (including sperm concentration, motility,
viability, morphology, DNA integrity and mitochondrial function),
2. endocrine changes (including hypogonadism, hyperinsuinemia and
hyperleptinemia) and
3. systemic and reproductive system inflammation and oxidative stress.
Impact of Obesity on Male Reproduction

55. dr. M. Alajami
Impact of Obesity on Male Reproduction

56. impair HPG axis function in obese men
dr. M. Alajami

57. dr. M. Alajami
֎ Maintaining sperm DNA integrity is essential for spermatozoa fertilizing
ability and successful pregnancy outcomes.
֎ Sperm DNA integrity is adversely affected in obesity.
֎ Increased (DFI) is accompanied by high BMI.
 BMI more than 25 kg/m2 corresponds to high sperm DFI.
(Benchaib et al., 2007)
Obesity and sperm DNA integrity
(Panner Selvam, Sengupta, & Agarwal, 2020).

58. dr. M. Alajami
֎ Sperm DNA fragmentation (SDF) induced by obesity alter the sperm functions
֎ Obesity-induced testicular oxidative stress is a possible mechanism.
֎ These cause oxidation of polyunsaturated fatty acids in sperm membrane, loss
of mitochondrial membrane potential and single- and double-strand SDF.
Obesity and sperm DNA integrity
Panner Selvam et al., 2020)

59. dr. M. Alajami
֎ ED have a positive correlation with male infertility.
֎ Obese men have a 1.5-fold increased chance of developing ED.
֎ Obesity may lead to erectile dysfunction by
1. reduction in testosterone levels
2. systemic inflammatory condition via release of inflammatory cytokines.
 directly induce endothelial cell dysfunction
 and via nitric oxide pathway.
3. linked pathogenic conditions, such as diabetes, hypertension and dyslipidemia
(Du Plessis et al., 2010)
Obesity and erectile dysfunction (ED)
(Yu, Li, Li, Zhong, & Mao, 2017)
(Shamloul & Ghanem, 2013)
(Seftel, 2006)
(Sarwer, Hanson, Voeller, & Steffen, 2018)

60. dr. M. Alajami
Mechanisms of obesity related male infertility

61. dr. M. Alajami
Low-grade systemic chronic inflammation associated with obesity

62. dr. M. Alajami
֎ ART outcomes of couples with an obese male partner:
1. decreased impregnation rate
2. decreased live birth rates
3. compromised infant health.
Male Obesity and ART Outcomes

63. dr. M. Alajami
Treatment male obesity infertility

64. dr. M. Alajami
Treatment male obesity infertility
dr. M. Alajami

65. dr. M. Alajami
֎ Reduced abdominal adiposity, independent of a change in BMI, reduce seminal
oxidative stress and SDF
֎ Improve DNA fragmentation a benefit on embryo, fetal and offspring
quality.
(Håkonsen et al., 2011)
1. Lifestyle modifications
(Mir, Franken, Andrabi, Ashraf, & Rao, 2018)

66. dr. M. Alajami
֎ Mediterranean diet:
 Rich in fruits, vegetables, antioxidants, nuts, seeds and fish. (antioxidant)
 improves sperm concentration, motility and morphology in humans.
(Karayiannis et al., 2017)
(Gaskins, Colaci, Mendiola, Swan, & Chavarro, 2012)
1. Lifestyle modifications

67. dr. M. Alajami
Mediterranean Diet

68. Mediterranean Diet
dr. M. Alajami

69. dr. M. Alajami
֎ Obesity is paradoxically associated with micronutrient deficiencies (MND)
through nutrient-poor foods and the increased requirements for antioxidants.
֎ Common MND in obesity includes vitamin D, selenium, vitamin C, zinc, vitamin
B1, β-carotenes, folate and vitamin E
֎ Supplementation with omega-3 fatty acids is associated with better testicular
function.
(Alhashem et al., 2014)
(Jensen et al., 2020)
1. Lifestyle modifications

70. dr. M. Alajami
֎ Antioxidant treatment
1. reduces DNA damage
2. improves fertility and ART outcomes (up to 4-times improvement)
3. reduces the risk of pregnancy complications and spontaneous abortions
֎ Antioxidant-rich nutrition is recommended as a primary source of the
antioxidants and micronutrients.
֎ supplementation of specific or combined antioxidant treatments considered.
(Maneesh & Jayalekshmi, 2006)
(Mora-Esteves & Shin, 2013)
1. Lifestyle modifications

71. dr. M. Alajami
Physical exercise
֎ a critical strategy to manage obesity and co-morbidities, improve overall health
and sense of well-being.
֎ Exercise induces
1. Rapid rise in testosterone, through increased pituitary activity,
2. Improved Leydig cell function
3. Reduction testosterone clearance.
4. Improve fertility parameters, including oxidative stress and DNA damage in
spermatozoon
(Sansone et al., 2018)
1. Lifestyle modifications
Physical exercise

72. dr. M. Alajami
Moderate exercise
 Improves sexual function and satisfaction in obese men, where increased fitness
correlated with sexual desire and satisfaction.
 Recommended as first-line treatment in erectile dysfunction.
(Sansone et al., 2018)
(Shamloul & Ghanem, 2013)
1. Lifestyle modifications
Moderate exercise

73. dr. M. Alajami
Moderate exercise
 excessive intensity or duration of exercise can be detrimental on male
reproductive outcomes (reduction in serum testosterone over time).
 intense exercise is not recommended
(Du Plessis et al., 2010)
1. Lifestyle modifications
Excessive intensity exercise
(Sansone et al., 2018)

74. 2. Prescription medication
dr. M. Alajami
֎ Metformin
 Improve semen parameters and fertility outcomes, (testicular weight and increased
numbers of spermatogonia, Sertoli and Leydig cells).
 By:
 Reduced apoptosis
 Protection against testicular inflammation
 Protection against oxidative stress.
(Ferreira et al., 2015).
(Ferreira et al., 2015; Ye et al., 2019).

75. 2. Prescription medication
dr. M. Alajami
֎ Testosterone replacement therapy (TRT)
 Excessive testosterone has a detrimental impact on spermatogenesis, primarily
through the negative hormonal feedback.
 TRT is not recommended for management of obese patients with desire fertility.
(Winter, Zhao, & Lee, 2014)
(Roth et al., 2008; Winter et al., 2014)

76. 2. Prescription medication
dr. M. Alajami

77. 2. Prescription medication
dr. M. Alajami
Aromatase inhibitor (such as Letrozole and Anastrozole)
֎ improvement of hypogonadism in obese males.
 suppress the conversion of testosterone to estrogen in obesity
 improve spermatogenesis and semen parameters.
 approval for use in male infertility is currently lacking (Roth et al., 2008)
(Stephens & Polotsky, 2013)

78. 2. Prescription medication
dr. M. Alajami
֎ Clomiphene citrate (selective estrogen receptor modulator)
 improve testosterone in hypogonadal obese males.
֎ Human chorionic gonadotropic (hCG), a LH analog
 increase intratesticular and serum testosterone levels and maintain
spermatogenesis in hypogonadal men,
 the impact on adiposity in males is not clear
(Bendre, Murray, & Basaria, 2015; Ring, Lwin, & Köhler, 2016)
(Ring et al., 2016)

79. 3. Surgical interventions
dr. M. Alajami

80. 3. Surgical interventions
dr. M. Alajami

81. 3. Surgical interventions
dr. M. Alajami
Bariatric surgery
֎ No positive impact of on male fertility parameters
֎ Potentially worsen semen parameters
 azoospermia and oligoasthenoteratozoospermia in the months following
the procedure.
 induced by the release of lipophilic toxic substances due to rapid weight loss, which include
endocrine disrupters stored in the excess adipose tissue through environmental exposures.
(Wei, Chen, & Qian, 2018).
(Reis & Dias, 2012; Wei et al., 2018).
(di Frega, Dale, Matteo, & Wilding, 2005; Sermondade et al., 2012)

82. dr. M. Alajami

83. dr. M. Alajami
Have a nice day