Defined as 1 year of attempted conception without success.
Defined as failure to achieve pregnancy after 12 months of regular unprotected intercourse with the same partner.
Affects one in 10 couples and is associated with frustration snd anxiety.
WHO reports the incident of infertility and reproductive age couples is one in six.
Because approximately half of these couples will conceive without intervention over the next 12 to 24 months, the term subfertility is also sometimes.
Lifetime prevalence of infertility in industrialized nations is 17-26%.
Self-reported infertility affects approximately 6% of married women age 15-44 years.
Affect more than 6 million couples.
For couples the major causes are female anatomic abnormalities, ovulatory dysfunction, idiopathic reasons and male infertility (Brassard M).
Ovarian aging is an important and irreversible factor as a cause of infertility.
With aging there is lower fecundity and oocytes develop defects in mitochondrial structure and function and have meiotic spindle dysregulation that increase rates of aneuploidy and miscarriage.
Rates of miscarriage are approximately 12% in women age 20 to 29 years, 25% by 40 years, 40% by 43 years, and 65% in females 45 years and older.
Evaluation of female fertility includes establishing the length of the menstrual cycle, gestational history, history of sexually transmitted diseases, medication exposure, weight changes and identifying exercise levels.
Laboratory evaluation for female infertility includes measurement of human chorionic gonadotropin levels, thyrotropin level, prolactin level, FSH level, estradiol level, dehydroepiandrosterone sulfate level, and free testosterone level.
Ovulation is confirmed by measuring progesterone level during the midluteal phase.
Male infertility is evaluated initially with semen analysis.
Almost half of all cases of male infertility are associated with genetic defects.
Approximately 20% of men with nonobstructive azoospermia have chromosomal abnormalities including sex chromosomal abnormalities such as Klinefelter’s syndrome, structural abnormalities such as translocations and inversions, and Y chromosome deletions.
Up to 20% of infertile males have a diagnosis of azoospermia.
80% of men with nonobstructive azoospermia have negative results on genetic testing.
There are several types of azoospermia with the most severe form being Sertoli-cell-only syndrome with a complete absence of germ cells.
Azoospermia with meiotic arrest suggest a milder type of infertility with spermatocyte stage arrest of germ cell formation.
Male infertility associated with a higher risk of prostate cancer.
Hemizygous TEX11 mutations are a common cause od meiotic arrest and azoospermia in infertile men.
Sertoli-cell-only syndrome and meiotic arrest affect seminiferous tubules.
A mild form of azoospermia, mixed testicle atrophy, has a variable degree of germ cell loss and sperm detected in some seminiferous tubules.
By one year of regular unprotected intercourse 85% of couples attempting conception will be successful, and at two years the percentage is 95%.
Three fourths of infertility cases are explainable, while the remainder are unexplained.
The majority of cases of female infertility are a result of ovulation or fallopian tube disorders, while other causes such as endometriosis, cervical abnormalities, and uterine abnormalities may be responsible.
The major cause of male infertility is due to a low number of functional sperm in the ejaculate.
In healthy couples probability of conception is 20-25% in one reproductive cycle.
Evaluation recommended after 1 year of unprotected intercourse without conception and should begin after six months in women older than 35 years.
Most evaluations will include a semen analysis, an assessment of ovulatory function, a uterine cavity assessment, and an assessment of tubal patency.
The likelihood of a live birth in women with infertility is less than 50%.
Couples with less than 3 years’ duration of infertility have a 1.8-fold higher probability of conceiving than those with longer duration.
The probability of a live birth is 1.5-fold higher if the female partner is younger than 30 years and has had a previous pregnancy.
Ovulation disorders are present in more than 25% of infertile female partners.
Low response to ovarian stimulation is a strong indicator of diminished ovarian reserve and infertility(Kwee J).
BRCA1 mutations are associated with occult primary ovarian insufficiency and may, in part, explained a link between infertility and breast/ovarian cancer risks (Oktay K ).
Ovulation disorders frequently respond to clomiphene citrate.
Approximately 20% of infertile female partners have tubal disease.
Distal tubal occlusion or partial occlusion may be addressed by laparoscopic or microsurgical treatment with a success rate of approximately 25%.
The usual treatment for women with tubal occlusion is in vitro fertilization.
In vitro fertilization is successful fewer than half of initiated cycles.
Endometriosis is found in 5-10% of infertile female partners.
With mild endometriosis spontaneous conception rate is 2-3% per month compared to the healthy monthly rate of 20%.
30% of infertile couples have unexplained infertility.
Mean prognosis for a live birth is 30-35% for couples with explained or unexplained infertility.
Treatment for unexplained fertility is 3 to 6 cycles of clomiphene citrate and intrauterine insemination.
Ovarian deterioration that occurs with advancing maternal age associated with infertility.
Rate of pregnancy for infertility drops more rapidly in women who are over the age of 35 years than in younger women.
Stress such as weight loss, eating disorders, excessive exercising, and psychological distress can suppress the hypothalamic-pituitary gonadal axis by inhibiting the hypothalamic pulsatile secretion of gonadotropin-releasing hormone (GnRH)-functional hypothalamic amenorrhea.
Female infertility frequently due to functional hypothalmic amenorrhea, defined as absence of menstruation, low or normal gonadotropin levels and hypoestrogenemia without organic abnormality.
Adminstration of exogenous pulsatile GnRH can restore the functionality of the hypothalmic-pituitary -gonal axis.
Leptin levels, a signal of fat reserve, are often low in hypothalmic amenorrhea.
Leptin relpacement can restore GnRH pulsatility.
In stress related amenorrhea, removal of the stressor can result in normal reproductive function.
Obese men have increased levels of inflammatory markers in their seminal fluid and lower sperm quality, both of which correlate with their body mass index (BMI):suggesting that chronic inflammation in male reproductive organs explains the link between obesity and reduced fertility.
Idiopathic hypogonadotropic hypogonadism is associated with an absence of puberty, infertility related to defects in GnRH secretion from the hypothalamus or defects in the action of GnRH on the pituitary gland.
When there is no identifiable male or female cause assistant reproductive technology, including in vitro fertilization and intracytoplasmic sperm injection, provides the best chance of success for pregnancy.
Among couples seeking infertility treatment, the use of folic acid and zinc supplementation by male partners, compared with placebo did not improve semen quality or couples’ live birth rates.