Infertility and Assisted

• Infertility


  Failure of a couple to conceive after 12 months of unprotected sexual intercourse. If the female partner is 35 years of age or older, evaluation should be initiated after 6 months of unprotected intercourse.
• In the United States, 1.2 million women (2% of couples with reproductive aged women) sought medical help in 2002 to become pregnant and 10% of women had received infertility services during their lifetime.
• Fecundability


  The ability to achieve pregnancy in one menstrual cycle
• The fecundity rate in a normal couple who has had unprotected intercourse is approximately 20% to 25% for the first 3 months, followed by 15% during the next 9 months. This means that 80% to 90% of couples are able to spontaneously conceive within 12 months.
• The fecundity rate of the cohort decreases over time and with increasing maternal age.
• For the remaining 10% to 20% of couples who are incapable of conceiving on their own within that time frame, the factors contributing to infertility vary widely.
• Contribution of male and female factors to infertility

  • 45-55% Female factor only
  • 35% Male factor only
  • 10-20% Combination male and female factors
  • 10% Unexplained infertility
• Most common identifiable female factors

  • Ovulatory disorders (32%)
  • Fallopian tube abnormalities including pelvic adhesions (34%)
  • Endometriosis (15%)
• Other factors that cause infertility

  • Uterine and cervical factors
  • Luteal phase defect
  • Genetic disorders
• Hypothalamic-pituitary-gonadal axis (HPGA)


  Disruption can result in menstrual disorders and infertility through impairment of folliculogenesis, ovulation, and endometrial maturation
• WHO classification of ovulatory disorders

  • WHO group 1: Hypogonadotropic hypogonadal anovulation (hypothalamic amenorrhea)
  • WHO group 2: Normogonadotropic normoestrogenic anovulation (polycystic ovarian syndrome [PCOS])
  • WHO group 3: Hypergonadotropic hypoestrogenic anovulation (premature ovarian failure, advanced maternal age)
  • WHO group 4: Hyperprolactinemic anovulation
• The most common ovulatory disorders that lead to infertility are PCOS and advanced maternal age.
• Oocyte aging


  An important factor affecting female fertility. The number of viable follicles continues to decline throughout the reproductive years and the rate of loss accelerates after the mid-30s.
• At the time of menopause, the ovary contains fewer than 1,000 follicles.
• Factors that result in decreased ovarian reserve and primary ovarian insufficiency

  • Tobacco smoking
  • Viruses
  • Radiation and chemotherapy
  • Autoimmune and genetic disorders
• The live birth rates for nulliparous women undergoing ART using fresh non-donor eggs exponentially decline after 35 years of age.
• If donor eggs are utilized, the live birth rate is determined by the age of the donor.
• PCOS


  The most common cause of oligo-ovulation and anovulation among all women and those presenting with infertility
• The prevalence of reproductive-age women with PCOS based on the NIH 1990 criteria is 6.5% to 8%.
• Risk factors for PCOS

  • Obesity
  • Insulin resistance
  • Diabetes
  • Infertility
  • Premature adrenarche
  • Positive family history among first-degree relatives
• Tubal disease and pelvic adhesions

  Result in infertility by preventing the transport of the oocyte and sperm through the fallopian tube
• Pelvic inflammatory disease (PID)


  The primary cause of tubal factor infertility
• In countries where infection by gonorrhea and Chlamydia is increasing and treatment is limited, tubal factor infertility is on the rise.
• Approximately 15% of infertile women have endometriosis.
• Endometriosis


  The presence of endometrial cells outside the uterine cavity, which can invade local tissues and cause severe inflammation and adhesions
• Infertility has also been diagnosed in women with minimal endometriosis and minimal to no adhesive disease.
• Uterine and cervical factors that can contribute to infertility

  • Submucosal fibroids
  • Polyps
  • Intrauterine synechiae (Asherman's syndrome)
  • Congenital malformations (especially uterine septums)
  • Endometrial abnormalities
  • Cervical stenosis
  • Cervicitis or chronic inflammation
• Risk factors for uterine factor infertility include conditions that predispose to intrauterine adhesions such as history of PID, infection after pregnancy loss, and multiple curettages of the uterus.
• Diethylstilbestrol (DES) exposure in utero also increases uterine factor infertility.
• Diethylstilbestrol (DES) exposure in utero increases uterine factor infertility
• DES was banned by the FDA in the United States in 1971
• The majority of women who had the potential for in utero exposure to DES have largely moved beyond the age of childbearing
• Cervical problems that can contribute to infertility

  • Structural abnormalities of the cervix
  • Cervicitis
  • Abnormal cervical mucous production
• Cervical stenosis


  May be iatrogenic and may result from cervical scarring after loop electrocautery excisional procedure (LEEP) conization, mechanical dilations, and from extensive laser or cauterization of the cervix
• Disruptions in normal mucus production can lead to difficulty in conceiving
• Luteal phase defect


  A controversial and poorly understood disorder that may begin with disruption of the HPGA, resulting in inadequate production of progesterone by the corpus luteum and subsequent delay in endometrial maturation, leading to impaired implantation following fertilization
• In couples in which no other cause of infertility can be determined, infertility may be due to genetic abnormalities
• The most common aneuploidy associated with female infertility is 45X (Turner syndrome)
• Symptoms related to ovarian, tubal, uterine, and cervical factors that can lead to infertility

  • Ovulatory dysfunction (amenorrhea, oligomenorrhea, menorrhagia)
  • PCOS (hirsutism, irregular menses, weight changes)
  • Endometriosis (cyclic pelvic pain, dysmenorrhea, dyspareunia)
  • Pelvic adhesions (pelvic pain)
• Uterine factor infertility


  May present with endometritis (pelvic pain and fever), submucosal fibroids and polyps (abnormal uterine bleeding), uterine anomalies like uterine septum (recurrent pregnancy loss), and cervical factor infertility (prior cryotherapy, conization, cervical dilations)