Infertility: The Age of Spermaggadon

Infertility is at its all-time high with one in six couples in Europe unable to conceive naturally. Some researchers suggest that by the year 2050 most couples would need to resort to IVF assisted pregnancies. So, what exactly is infertility and how are we disrupting fertility?

Diet, Obesity and Environment
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Long-term consumption of Western diet which comprises high calorie, high fat and low fiber content may increase the risk of Type II Diabetes Mellitus, cardiovascular diseases, chronic inflammatory diseases, cancers and also result in infertility. 
​A group of researchers from North Carolina experimented on a mice model to see if there is a correlation between obesity and infertility. They fed the experimental group with lard accounting for 60% more kilocalories than the normal mice food. They found that the high fat fed mice showed significantly low rates of fertility with low sperm movement and activity. They also showed that mating of obese male mice with normal female mice resulted in reduction of the number of offspring conceived [1].

In the human male population, according to a Danish study, a lower sperm count was seen in both overweight and underweight populations. Faulty sperm production causing infertility in obese male population might be a result of DNA fragmentation and damage [2][3]. 

Poly-cystic ovarian syndrome or PCOS is commonly associated with obese or overweight females and may result in infertility in women. Studies have shown that women with higher BMI are four times more likely to experience menstrual cycle irregularities when compared to women with normal BMI. Also, women with high pre-pregnancy weight are at risk of pregnancy complications such as gestational diabetes mellitus, preeclampsia and also recurrent miscarriages and stillbirths [4].

Environmental factors when acting together with genetic and dietary habits might further increase the risk of failure in conception. Exposure to certain environmental chemicals usually found in pesticides, plastics, tobacco products, and even trace amounts in food and drinking water may interfere with hormonal activity and normal cell functioning, causing higher risk of infertility in both sexes [5].

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Age: the ticking clock

In the last decades the average age of women having a first child has gone up to 30 years, especially in high income countries due to a number of reasons including higher education, professional growth along with high economic and financial responsibilities that arise with having children. However, research shows that by 35 years of age, the fertility rate in women goes down to 66% and it further decreases to 44% by 40 years of age. Also, pregnancy at an advanced age is more likely to result in complications with long term health consequences for the mother and the baby. 

Studies have shown that the average paternal age for having first child has risen from 27.4 years to 30.9 years in America. Similar trends have been seen in studies done in Germany and the UK [6]. Male sex hormones start declining by a small percentage per year after 50 years of age, contributing to infertility. There are limited studies that indicate a relationship between high paternal age and lack of fertility. A few studies have shown that men over 50 years of age have lower pregnancy success rates even when their partners were significantly younger [7],[8].

Medically-Assisted Reproduction

Many couples who are unable to conceive naturally resort to in vitro fertilization (IVF) assisted pregnancy. IVF can be defined as a medical procedure whereby an egg is fertilized by sperm in a test tube or elsewhere outside the body. IVF therapies are available in the form of intrauterine insemination, in vitro fertilization, IVF using donor eggs, and intracytoplasmic sperm injection where one sperm is directly injected into the egg.

​The steps to one IVF cycle are shown in the following image [9]:

IVF-Assisted Pregnancy & Recurrent Miscarriages 

Many couples who conceive with the help of medical procedures such as IVF may still remain childless due to recurrent spontaneous miscarriages [10]. There are several factors that might result in early pregnancy loss. A successful implantation is for example influenced by the health and genetic makeup of the embryo. 

Source: click on image or see [13]

​In certain IVF assisted pregnancies, the embryo may not be recognized by the immune system, which results in early miscarriage. This might also be the case in assisted pregnancy using donor eggs. Natural Killer (NK) cells are a type of immune cells that play a big role in pregnancy maintenance. Natural killer cells are the primary cells for recognizing and killing invading cells, and pathogens that might be harmful to the body. There have been controversial opinions of obstetrics researchers regarding the role of NK cells and fertility. One school of thought is that too many NK cells “attack” and are likely to destroy the embryo in IVF assisted pregnancies, however many believe that uterine NK cells lack the ability to attack the embryo since the uterus is in contact with the placenta and not the embryo. Uterine NK cells are abundantly available during the first trimester of pregnancy and play a role in early placental development. They might also be linked to other pregnancy complications such as preeclampsia [11]. However, the immune system is complex, and any one variable cannot be completely responsible for pregnancy outcome and further research is needed to link the effects of immunity, infertility and recurrent miscarriages [12].

In other studies, researchers have found that in women over 35 years of age, egg aneuploidy or having an abnormal number of chromosomes in cells is strongly associated with pregnancy loss and low chances of implantation in IVF assisted pregnancies [13].

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Is IVF the only solution?

Getting IVF can be an expensive affair with couples in American spending an average of $12,000 for one cycle of treatment [14]. But before we jump towards expensive medical or technological procedures, maybe we can fix some of the problems that we can control.

Many studies have investigated consumption of macro and micronutrients such as Folic Acid, Vitamin D, carbohydrates, fatty acids and soy products, however the results haven’t been clear. Including certain anti-inflammatory herbs and spices such as turmeric, ginger, garlic and black pepper in diet might affect immune system and increase chances of conception [15]. These mentioned methods might not work but I can assure you that tiger bones, amazon rainforest frogs and snake infused alcohol do not increase fertility.

Fertility experts believe that for some couples mere changes in lifestyle such as a healthy, balanced diet, moderate exercise, cutting back on tobacco consumption and cutting back on sugar might make a difference.

 It is a long road from infertility to pregnancy and parenthood, mostly filled with frustration, anguish and uncertainity, however, I am certain that continued research in the field of fertility and reproductive sciences will unlock the mystery of infertility, fertilization and successful pregnancies for couples worldwide. 

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Author: Samprikta Manna is an iPlacenta Early Stage Researcher. Read her earlier blog post here. 

References:

[1] Ghanayem, B. I., et al. (2010). "Diet-Induced Obesity in Male Mice Is Associated with Reduced Fertility and Potentiation of Acrylamide-Induced Reproductive Toxicity1." Biology of Reproduction 82(1): 96-104.

[2] Cabler, S., et al. (2010). "Obesity: modern man's fertility nemesis." Asian journal of andrology 12(4): 480-489.      

[3] Jensen, T. K., et al. (2004). "Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men." Fertility and Sterility 82(4): 863-870.

[4] Zain, M. M. and R. J. Norman (2008). "Impact of Obesity on Female Fertility and Fertility Treatment." Women's Health 4(2): 183-194.

[5] Perheentupa, A. (2019). "Male infertility and environmental factors." Global Reproductive Health 4(2).

[6] Khandwala, Y. S., et al. (2017). "The age of fathers in the USA is rising: an analysis of 168 867 480 births from 1972 to 2015." Human Reproduction 32(10): 2110-2116.

[7] Ford, W. C. L., et al. (2000). "Increasing paternal age is associated with delayed conception in a large population of fertile couples: evidence for declining fecundity in older men." Human Reproduction 15(8): 1703-1708.           

[8] Group, E. C. W. (2005). "Fertility and ageing." Human Reproduction Update 11(3): 261-276.

[9] https://www.wisdomancient.com/2019/06/what-about-step-by-step-guide-to-ivf.html (accessed  09/06/2021). For a more detailed description, see: https://www.mayoclinic.org/tests-procedures/in-vitro-fertilization/about/pac-20384716 (accessed 09/06/2021)

[10] Tamhankar, V. A., et al. (2015). "A Comparison of Pattern of Pregnancy Loss in Women with Infertility Undergoing IVF and Women with Unexplained Recurrent Miscarriages Who Conceive Spontaneously." Obstetrics and gynecology international 2015: 989454-989454.

[11] Moffett-King, A. (2002). "Natural killer cells and pregnancy." Nature Reviews Immunology 2(9): 656-663.

[12] Seshadri, S. and S. K. Sunkara (2014). "Natural killer cells in female infertility and recurrent miscarriage: a systematic review and meta-analysis." Human Reproduction Update 20(3): 429-438.

​[13] http://denverholisticmedicine.com/advanced-maternal-age (accessed 03/06/2021)

[14] https://www.vox.com/the-goods/2020/4/14/21216325/ivf-fertility-treatment-cost-best-money (Accessed on 09/06/2021)
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[15] https://glenvillenutrition.ie/immune-related-infertility/ (Accessed on 09/06/2021)