The process from conception to birth is so intricate and mind-boggling in complexity; it is no wonder that things can go wrong. The list of causes of infertility that affects both the male and female is extensive. Sometimes answers are found quickly, and solutions are easy. Sometimes the specific cause remains elusive. Some of the causes of female and male infertility are listed below.

Causes of female infertility

Causes of female infertility include hormonal imbalances, ovulatory disorders, endometriosis, fallopian tube damage, benign uterine fibroids, and pelvic adhesions.

Hormonal imbalances

Hormonal imbalances may result in subtle flaws in egg development and ovulatory dysfunction, which accounts for many instances of infertility and miscarriages. Hormones that play a role in ovulation and fertilization include progesterone, estrogen, androgens, thyroid hormone, prolactin, insulin, steroids, and other pituitary hormones (LH and FSH).

Disorders of the thyroid gland, either too much thyroid hormone (hyperthyroidism) or too little (hypothyroidism), can interrupt the menstrual cycle and cause infertility.

Many factors cause hormone imbalances. For example, age, general health, amount of exercise, or malfunction of any of the hormone producing organs. Conditions such as sleep apnea may lead to insulin-resistance, which can lead to infertility.

Ovulation disorders

• Hypothalamus-pituitary imbalance . Disruption in this part of the brain, which regulates ovulation, can result in abnormal levels or secretion patterns of pituitary hormones such as luteinizing hormone (LH) and follicle-stimulating hormone ( FSH). Even slight irregularities in the hormonal balance can prevent the ovaries from producing a viable egg. Factors that may affect this part of the brain include stress, tumors, excessive exercise, nutrition, and some medications. Amenorrhea can be due to a lack of hormones from the hypothalamus-pituitary system.
• Insulin-resistance , with or without obesity, in pre-diabetic men and women, is a common cause of infertility.
• Polycystic ovary syndrome (PCOS). With PCOS, the ovaries contain numerous egg sacks (follicles) which do not regularly release the eggs (ovulate), because of a hormonal imbalance. It may be associated with insulin resistance and obesity. When an ultrasound examination indicates possible PCOS, it must be confirmed and diagnosed with a blood test.
• Early menopause (premature ovarian failure). Early menopause is the absence of menstruation and the early depletion of ovarian follicles before age 40. Although the cause is often unknown, certain conditions are associated with early menopause such as endometriosis, immune system diseases, cancer treatment, or smoking.
• Elevated prolactin (hyperprolactinemia). The hormone prolactin stimulates breast milk production. Occasionally, women who are not pregnant or nursing may have high levels of prolactin, which suppresses ovulation. Causes include hyperplastic pituitary cells, pituitary tumor, and certain drugs. Milk flow not related to pregnancy or nursing can be a sign of high prolactin.

Functional Abnormalities

These include damage due to endometriosis, tubal blockage, fibroids, and polyps inside of the uterine cavity.

Endometriosis is a condition where uterine tissue implants and grows outside of the uterus. These implants respond to the hormonal cycle and grow, shed and bleed in synchrony with the lining of the uterus every month. Besides causing discomfort and pain, these abnormal cells can cause inflammation and damage to ovaries, and fallopian tubes, and reduce the number of available eggs. Pelvic pain and infertility are common in women with advanced endometriosis.

Fallopian tube damage or blockage usually results from inflammation of the fallopian tube (salpingitis). Chlamydia, a STD, is the common cause. Tubal inflammation may be asymptomatic or may cause pain and fever. Tubal damage may result in an ectopic pregnancy where the fertilized egg is unable to make its way through the fallopian tube to implant in the uterus. Only one episode of tubal infection may cause infertility problems. The risk of ectopic pregnancy increases with each occurrence of tubal infection.

Fibroids and polyps may present as benign masses on the inside of the uterus and are common in women in their 30s and 40s. It may compromise embryo implantation or even act as an IUD. Rarely, they may cause infertility by blocking the fallopian tubes.

Pelvic adhesions are bands of scar tissue that bind organs after pelvic infection, appendicitis, or abdominal or pelvic surgery. This scar tissue formation may impair the ability of egg and sperm to meet.

Developmental and genetic malfunction of the uro-genital tract such as the absence of a cervix or malformed uterus.

General Health

• Age. Women’s reproductive ability diminishes significantly after age 34. The golden age for reproduction is equal or less than 34 years
• Diet: Diet affects every aspect of our general health. Body cells can not function properly in an acidic and toxic environment. When the diet is nutrient poor and chemically loaded, the body eventually becomes toxic and diseased. Specific issues include excessive caffeine intake and deficiencies in nutrients such as vitamin C, selenium, zinc, and folate.
• Lifestyle : Excessive stress, anxiety, lack of sleep and exercise, or too much exercise all adversely affect fertility. Infertility itself can sometimes become a long term, discouraging problem, producing more stress.
• Alcohol or drug dependency can be associated with poor health and reduced fertility.
• Diseases : Diseases affecting reproduction can be infectious (e.g. repeated bouts of sexually transmitted diseases, viral infections like mumps etc.) or inflammatory (e.g. auto-immune diseases) Medical conditions associated with delayed puberty or amenorrhea, such as Cushing's disease, sickle cell disease, kidney disease and diabetes, can affect a woman's fertility.
• Medications . Temporary infertility may occur with the use of certain medications. In most cases, fertility is restored when the medication is stopped.
• Environmental exposure of pesticides and other chemicals like lead, can affect fertility. Many cosmetic products contain chemicals that can be detrimental to female reproduction.

Cancer and cancer treatment

Cancer of the reproductive organs (ovarian, uterine, and cervical cancer), or of the hypothalamus-pituitary gland in the brain, can cause reproductive problems. Consequently, both radiation and chemotherapy treatment for any cancer can impair oocyte development, sometimes causing permanent, irreversible The closer radiation treatment is to the ovaries, the higher the risk of infertility.

Genetic abnormalities

A genetically flawed embryo may be unable to implant, can result in a miscarriages or can even result in babies born with genetic abnormalities. Parents, who have a family history of genetic abnormalities, should address the issue before having children. Pre-implantation Genetic Diagnosis (PGD) can be a lifesaving tool to assure that only normal embryos are transferred.

Main categories of genetic abnormalities that affect fertility include:

• Up to 80% of all embryos from fertile and infertile couples are genetically not viable. This number which increases with age is a result of human reproductive inefficiency and mostly does not suggest any genetic problems with the intended parents.
• Translocation. The embryo has too much or too little of a specific chromosome which is typically presented as an inability to conceive or as a recurrent miscarriage. This is frequently the result of one parent being a carrier of a balanced chromosome translocation. This condition can be diagnosed and circumvented with PDG.
• Incorrect number of chromosomes such as Down’s and Edward Syndrome, or embryos with multiple chromosomal imbalances (aneuploidy), which prevent development after the 8-cell stage. Mostly this leads to the inability of an embryo to implant and less frequently to an affected baby. Parents usually are not responsible or acting as carriers for these conditions. PGD can be used to identify normal embryos.
• Single gene disorders include Cystic Fibrosis and Polycystic Kidney Disease. One or both intended parents may be a carrier of certain single gene disorder, which can result in affected embryos. PGD is very helpful to identify normal embryos.

Representation of a DNA molecule unwinding from a chromosome inside the nucleus of a cell. (Not to scale) Courtesy: National Human Genome Research Institute

Common causes of male infertility

These include abnormal sperm production/ function, impaired delivery of sperm, general health and lifestyle issues, and overexposure to environmental toxins.

Impaired production of sperm

Low sperm concentration. 20 million or fewer sperm per milliliter of semen indicates low sperm concentration. (A normal sperm concentration is greater than or equal to 20 million sperm per milliliter of semen.) Only rarely will the testicles completely fail to produce sperm. Causes of low sperm count include:

• Health and lifestyle issues that lower sperm count.
  • Overheating the testicles. Frequent use of saunas or hot tubs can elevate core body temperature, which may impair sperm production and reduce the sperm count.
  • Substance abuse. Cocaine or marijuana may temporarily lower the number and quality of sperm.
  • The use of certain drugs can also contribute to infertility. For example, anabolic steroids, testosterone injections which are frequently taken by body builders and performance athletes, can cause the testicles to shrink and sperm production to decrease.
  • Tobacco smoking. Men who smoke may have a lower sperm count than do those who do not smoke.
  • Excessive or prolonged emotional stress may interfere with hormones needed to produce sperm, lowering the sperm count.
• Testicular abnormalities . Problems include testicular inflammation/infection with resultant testicular scar tissue. Varicocele (varicose vein in the scrotum that may prevent normal cooling of the testicle), or an undescended testicle (exposed to the higher internal body temperature) may also contribute to lower sperm production.
• Hormonal imbalances : Abnormalities of the hypothalamus-pituitary system which produces FSH and LH, as well as other hormonal deficiencies can lower sperm production.

Impaired function of sperm

Abnormal shape and movement of sperm will prevent the sperm to quickly and accurately reach or penetrate the egg. Causes include:

• Infections such as sexually transmitted diseases ( STD’s) and mumps, or inflammation of the testicles, prostate, urethra, or epididymis can temporarily or permanently affect movement/motility of the sperm.
• Anti-sperm antibodies . Following surgical blockage of part of the vas deferens for male sterilization (vasectomy), the body usually produces antibodies against sperm that weaken or disable them. These antibodies may also complicate the reversal of a vasectomy.
• Too long periods of abstinence (>5 days) , results in sperm that is old.

Impaired delivery of sperm to the egg

Causes may include:

• Impotence, erectile dysfunction, premature ejaculation, painful intercourse, psychological and/or relationship issues, and incorrect timing can contribute to infertility. Some lubricants can be toxic to sperm.
• Retrograde ejaculation occurs when semen enters the bladder rather than emerging out through the urethra. Retrograde ejaculation can be a result of diabetes, bladder, prostate or urethral surgery or because of the use of certain medications.
• Blockage of epididymis or ejaculatory ducts . Some men are born with blockage of the epididymis or ejaculatory ducts. Men with cystic fibrosis, or who are carriers of cystic fibrosis often have a missing or obstructed vas deferens. Repeated bouts of sexually transmitted diseases (STDs), such as Chlamydia and Gonorrhea, can cause scarring and block sperm passage.
• The absence of ejaculate may occur in men with spinal cord injuries or diseases.
• Abnormalities of the female genital tract e.g. toxic mucous and anatomical malfunction.

General health issues that affect male fertility

• Age . Older men may be less fertile.
• Diet: Body cells can not function properly in an acidic and toxic environment. When the diet is nutrient poor and chemically loaded, the body eventually becomes toxic and disease follows. Specific issues include excessive caffeine intake, and deficiencies in nutrients such as vitamin C, selenium, zinc, and folate.
• Lifestyle: Excessive stress, anxiety, lack of sleep and exercise all adversely affect fertility. Infertility itself can sometimes become a long term, discouraging problem, producing more stress.
• Alcohol or drug dependency can be associated with poor health and reduced fertility.
• Diseases: Diseases affecting reproduction can be infectious (e.g. repeated bouts of sexually transmitted diseases, viral infections like mumps etc.) or inflammatory (e.g. auto-immune diseases) Certain conditions, such as diabetes, thyroid disease, Cushing's syndrome, or anemia may affect fertility.
• Environmental exposure of pesticides and other chemicals. Herbicides and insecticides may cause female hormone-like effects in the male body and may be associated with reduced sperm production and testicular cancer. Lead exposure may also cause infertility.

Cancer and cancer treatment

Testicular or prostate cancer can cause reproductive problems. Both radiation and chemotherapy treatment for any cancer can impair sperm production, sometimes causing irreversible damage to the germ cells responsible for producing sperm.

Genetic abnormalities

Genetic abnormalities can be a cause of a low sperm count and or weak sperm. Parents, who have a family history of genetic abnormalities, should address the issue before having children. Pre-implantation Genetic Diagnosis (PGD) can be a lifesaving tool to assure that only normal embryos are transferred.

Main categories of genetic abnormalities that affect sperm and embryos include:

• Microdeletions or abnormalities of the Y-chromosome can be the cause for low sperm concentrations (less than 5million/ml). Genetic testing may be able to detect subtle changes.
• Translocation. This is where the embryo has too much or too little of a specific chromosome. This typically is presented as an inability to conceive or as a recurrent miscarriage.
• Incorrect number of chromosomes such as Down’s and Edward Syndrome, or embryos with multiple chromosomal imbalances (aneuploidy), which prevent development after the 8-cell stage.

Single gene disorders that may affect couples include Cystic Fibrosis (CF) and Polycystic Kidney Disease. Most importantly, men who are carriers of the CF gene may have an incomplete vas deference. This means that even though normal sperm are produced, there is no intact pathway to get these sperm to the outside. Testicular or epididymal sperm extraction with ICSI and IVF is necessary to join the sperm and egg. One or both intended parents may be a carrier of certain single gene disorders, which can result in affected embryos.

23 pairs of human chromosomes Courtesy: National Human Genome Research Institute