Infertility

Infertility is “a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse (WHO-ICMART glossary^*). There are two kinds of infertility - primary and secondary:

Primary infertility means that the couple has never conceived. Secondary infertility means that the couple has experienced a pregnancy before and failed to conceive later. Globally, most infertile couples suffer from primary infertility.

Sexually transmitted infections (STIs) are the leading preventable cause of infertility by causing 70% of pelvic inflammatory diseases responsible for tubal damage. Low fertility is becoming more common worldwide, particularly in many urban settings where women are planning their first babies at older ages.

Infertility affects up to 15% of reproductive-aged couples worldwide. According to World Health Organization estimate the overall prevalence of primary infertility in India is between 3.9 to 16.8%. In Indian states prevalence of infertility varies from state to state such as 3.7 per cent in Uttar Pradesh, Himachal Pradesh and Maharashtra, to 5 per cent in Andhra Pradesh, and 15 per cent in Kashmir and prevalence varies in same region across tribes and caste.

The inability to have children affects couples and causes emotional and psychological distress in both men and women. Despite the various social, psychological, economic and physical implications, infertility prevention and care often remain neglected public health issues, or at least they rank low on the priority list, especially for low-income countries that are already under population pressure. But in recent years there is increased awareness to integrate infertility prevention, care and treatment into the basic health care services.

References-

* www.who.int/reproductivehealth/publications/infertility

www.who.int/reproductivehealth/topics/infertility/

icmr.nic.in/ijmr/2011/

www.who.int/bulletin/volumes/

www.ncbi.nlm.nih.gov/pmc/articles/

www.who.int/reproductivehealth/topics

For a woman, infertility (or a state of subfertility) can manifest itself as either (WHO):

• the inability to become pregnant
• an inability to maintain a pregnancy
• an inability to carry a pregnancy to a live birth.

Reference-

www.who.int/reproductivehealth/topics/infertilit

Infertility can be caused by both men and women factors. About a third of infertility problems are due to female infertility and another third are due to male infertility. In remaining cases infertility may be due to problems in both partners or the cause is unclear.

Female infertility can be caused by a number of factors:

(a)Damage to fallopian tubes: Damage to the fallopian tubes (carry the eggs from the ovaries to the uterus) can prevent contact between the egg and sperm. Pelvic inflammatory diseases (PID) caused by various infections, endometriosis, pelvic surgery may lead to damage to fallopian tubes. Sexually transmitted infections (STIs) are the common cause of PIDs.  

(b)Disturb ovarian function/hormonal causes: Synchronized hormonal changes occur during the menstrual cycle leading to the release of an egg from the ovary (ovulation) and the thickening of the endometrium (inner lining of the uterus) in preparation for the fertilized egg (embryo) to implant inside the uterus. Difficulty in ovulation is seen in following conditions-

• Polycystic ovary syndrome(PCOS) Polycystic ovary syndrome is the common cause of female infertility. PCOS interferes with normal ovulation.
• Functional hypothalamic amenorrhea: Excessive physical (common in athletes) or emotional stress may result in amenorrhoea (absence of periods).
• Diminished ovarian reserve or premature ovarian aging: women with diminished ovarian reserve may experience difficulty in conceiving, (though blood test will show elevated follicular stimulating hormones).
• Premature ovarian insufficiency: Female ovaries stop working before she is 40 years of age. The cause can be natural or it can be a disease, surgery, chemotherapy, or radiation.

(c)Uterine causes: Abnormal anatomy of the uterus; the presence of polyps and fibroids may lead to infertility.

(d)Cervical causes: A small group of women may have a cervical condition in which the sperm cannot pass through the cervical canal due to abnormal mucus production or a prior cervical surgical procedure.

Male factors causing infertility-

More than 90% of male infertility cases are due to low sperm counts, poor sperm quality, or both. The remaining cases of male infertility can be caused by number of factors including anatomical problems, hormonal imbalances, and genetic defects. Sperm abnormalities include:

• Oligospermia (low sperm counts) /Azoospermia (no sperms): sperm count less than 20 million/ml is termed as oligospermia whereas azoospermia refers to the complete absence of sperm cells in the ejaculate.
• Asthenospermia (Poor sperm motility): If 60% or more sperms have abnormal motility (movement is slow and not in straight line) it is termed as asthenospermia and may cause infertility.
• Teratospermia (abnormal sperm morphology): about 60% of the sperms should be normal in size and shape for adequate fertility.

Different factors including congenital birth defects, diseases (such as mumps), chemical exposure, and life style habits can cause sperm abnormalities.

Factors that affect the fertility of both sexes include the following:

• Environmental/occupational factors
• Toxic effects related to tobacco, marijuana, or other drugs
• Excessive exercise
• Inadequate diet associated with extreme weight loss or gain
• Advanced age 

References-

www.cdc.gov/reproductivehealth/infertility

www.webmd.com/infertility-and-reproduction/guide

umm.edu/health/medical/reports/articles/infertility

emedicine.medscape.com/article/

Both male and female factors can contribute to infertility. A detailed medical history, physical examination and investigations are needed to assess the cause of infertility.

Evaluation of infertility includes following steps:

(a) History taking: Couples with infertility problem are interviewed separately as well as together to know about important facts with full history taking. Full history includes: present history; menstrual and obstetric history (in female partner); contraceptive and sexual history; family and past history. 

(b)Clinical examination: Full clinical examination of both partners is required for detection of any physical problem. It includes general examination along with examination of chest, breast, abdomen, and genitalia. It helps to health care professional to make a provisional diagnosis. Investigations are advised to prove the clinical diagnosis and to exclude other close possible causes.

(c) Investigations: Infertile couples are usually advised to start their investigations after 12 months of trying to conceive or after six months if the female partner is more than 35 years old or immediately if there is an obvious cause for their infertility or subfertility.

As the major causes of infertility are sperm abnormalities, ovulation dysfunction, and fallopian tube obstruction, the preliminary investigations for the infertile couple should be focused on:

Semen analysis: It should be done after 72 hours of sexual abstinence and two analysis should be advised with 3 months apart at the same lab.(Results may be interpreted for its volume, sperm count, motility, and morphology according to the WHO reference values*).

Female partner

• Detection of ovarian function:
• Hormonal assay (early follicular FSH and LH levels, and mid-luteal progesterone levels),
• Transvaginal ultrasonography is used for detection of ovulation in females and any abnormality in uterus and adnexa (adjoining anatomical parts of the uterus).  
• Evaluation of tubal patency:
  •  Hysterosalpingography (HSG): It is a radiological procedure. The dye is injected in to the uterus through the cervix and simultaneously X-Ray pictures are taken to see the movement of dye in to the fallopian tubes. Spilling of dye into the abdominal cavity shows that tubes are patent.
• Advanced investigations-
  • Hormonal assay: Thyroid function test, prolactin levels, testosterone, and other tests if polycystic ovary syndrome is suspected.
  • Laparoscopy is a surgical procedure used to visualize abdominal and pelvic organs (uterus, fallopian tubes and ovaries).
  • Hysteroscopy is indicated for intrauterine space-occupying lesions detected on HSG
  • Chromosomal karyotyping is used for suspected genetic disorders.

Male partner-

• Hormonal assay: FSH, LH, Testosterone, TSH and Prolactin (for male with abnormal seminal analysis and suspected endocrine disorder)
• Testicular biopsy: A fine-needle aspiration biopsy to differentiate between obstructive and non-obstructive azoospermia.
• Chromosomal karyotyping is used for suspected genetic disorders.

References-

www.ncbi.nlm.nih.gov/pmc/articles/

* apps.who.int/iris/bitstream/

Management of infertility ranges from counseling and advice to medications and surgery.

Counseling of both partners is an important aspect in the management of infertility with medical and psychological support to the couple. Counseling is provided for the healthy life style measures such as:

• Healthy eating habits-
• Adding more whole-grain products, fruits, vegetables.
• Limiting processed foods and foods with added sugars, eating a diet low in cholesterol and saturated fats
• Promote regular exercise
• No smoking (avoid passive smoking)
• Limit alcohol intake
• Maintain healthy weight
• Folic acid supplementation in women
• Advice on rubella vaccination if seronegative
• Treatment of Psycho-sexual problems

Specific treatment of disease that causes infertility- Whatever cause is detected during investigations relating to female or male partner, treatment is given accordingly. Management of STIs and PCOS can be viewed on www.nhp.gov.in.

When initial treatments don't work, couple may decide for assisted reproduction technology.

Assisted reproduction techniques (ART):

• Intrauterine insemination (IUI): IUI is the placement of a man's sperm into a woman's uterus using a long, narrow tube. IUI may be used in the following conditions.
• Defects of cervix
• Low sperm counts
• Sperm with low motility
• Erection problems in male partner
• Retrograde ejaculation (a condition in which sperms are deposited in to the bladder instead of going out through the urethra)
• Women who have scarring or defects of the cervix.

IUI is of two types

• artificial insemination by husband (AIH);
• donor insemination (DI).
• In vitro fertilization (IVF): In vitro fertilization, eggs and sperm are taken from the couple and are incubated together in a dish in a laboratory to produce an embryo. Medical specialist places the embryo into the woman's uterus, where it may implant and develop in a successful pregnancy.
• Gamete intrafallopian transfer (GIFT): in this procedure fertilization occurs naturally after eggs and sperm are placed inside the fallopian tube.
• Zygote intrafallopian transfer (ZIFT): In ZIFT fertilized eggs are transferred to fallopian tube within 24 hours after fertilization.   
• Intracytoplasmic sperm injection (ICSI): In this procedure single sperm is injected in to mature egg. It is used to treat sperm related infertility problems.   

Surrogate and gestational carriers-If a woman is unable to carry a pregnancy to term, the couple may choose a surrogate or gestational carrier.

• A surrogate is a woman inseminated with sperm from the male partner of the couple. The resulting child will be biologically related to the surrogate and to the male partner. Surrogacy can be used when the female of the couple does not produce healthy eggs that can be fertilized.
• A gestational carrier is implanted with an embryo that is not biologically related to her. This alternative can be used when a female partner produces healthy eggs but is unable to carry a pregnancy to term. Egg or sperm donation can be used in this situation.

References-

www.acog.org/~/media

(b)Eat a balanced diet which should include whole grains, pulses, fresh fruits and vegetables, low fat milk products. Limiting consumption of sugar, alcohol, caffeine, no smoking including passive smoking can have a beneficial impact on a couple’s ability to conceive.

(c)Participating in moderate exercise can help improve menstrual regularities and overall health, whereas sometimes excessive exercise can disturb menstrual cycle as seen in competitive athletes practicing intense training sessions.

hwww.cdc.gov/reproductivehealth/infertility/

www.nhs.uk/news/2009/11November/Pages/get-fit-exercise-infertility