Evaluation and Treatment of the Infertile Couple
Initial Consultation
You and your partner should be interviewed during first visit. The doctor should ask you about you and your partner's age, duration of infertility, previous pregnancies and surgeries, coital frequency, pain during intercourse, erection failure, lack of orgasm or lack of libido and problems encountered during intercourse.
Problems are assessed and treated.
Obese women are at higher risk for infertility as they are less likely to ovulate i.e. release an egg.
Long-term use of nonsteroidal anti-inflammatory drugs can lead to infertility.
Smoking also can lead to infertility.
Age
Women fertility and pregnancy rates decreases after reaching 30 years of age.
By the age of 40, a woman's monthly fecundity is less than 5%.
Poor oocyte (egg) quality is the main factor responsible for this decline in pregnancy rate.
Male fertility also diminishes with age. Sperm quality declines, and the frequency of ejaculation decreases as men grow older.
Nearly 50% of the infertility experienced by couples older than 40 years is caused by problems associated with advancing age.
Therefore, age is an independent risk factor that is instrumental in determining a couple's chance of achieving a successful pregnancy.
The duration of infertility
Is an important independent risk factor as the age of the couple. The longer the duration of infertility, the lower is the probability of achieving a successful pregnancy.
Male Infertility
Is the primary cause in one third of infertile couples.
Causes:
Testicular injury
Testicular Infection
Testicular Surgery
Testicular Radiation
Testicular Chemotherapy
Hypospadius 'urethral opening on the lower surface of the penis'
Cryptorchidism (un-descended testis)
Varicoceles.
If any of the above 3 anomaly is present the patient should see urologist for evaluation and treatment.
After the initial physical examination, a semen analysis should be performed.
The specimen is collected after 48-72 hours of coital abstinence and evaluated within 3 hours after collection.
If any abnormality is noted two additional semen analyses should be performed 2 weeks apart.
Persistent abnormalities may need
Urologic referral
Testing for diabetes mellitus, prolactin elevation and chromosomal abnormalities
Sperm penetration assay to assess penetration
Sperm immunobead-binding assay to assess motility
Idiopathic oligospermia 'no cause of reduced sperm number' is the most common cause of infertility in men. There is no cure for this problem. Treatment is in vitro fertilization 'IVF' with microinjection of sperm into egg intracytoplasmic sperm injection 'ICSI'.
This technique can achieve fertilization rates as high as 65% even in sever cases of oligospermia.
If semen tests are normal and the female partner's tests are normal, infertility is called unexplained.
Female Infertility
Tubal, Uterine and Pelvic Factors
Cause one third of the infertility experienced by couples and forty percent of the infertility in women.
Sexually transmitted diseases, pelvic inflammatory disease, appendicitis with rupture, endometriosis, ectopic pregnancy, uterine, fibroid, tubal or ovarian surgery can cause tubal or pelvic damage. Fibroids rarely cause infertility but may cause recurrent early pregnancy loss and preterm labor.
Hysterosalpingography (HSG) is one of the initial diagnostic tests used to evaluate uterine, tubal, and pelvic abnormalities. This test is performed during the five days starting from the end of menstrual flow 'cycle day 5 to 10'.
Patients who are known to be anovulatory may forgo an initial HSG. If ovulation induction is successfully attempted for at least three consecutive cycles and conception does not occur, HSG should be performed.
Prophylactic treatment for chlamydial infection should be given to patients investigated with HSG. Oral Doxycycline, 100 mg twice daily for 7 days, is effective.
HSG can diagnose:
Abnormalities of uterine filling: submucous fibroids, polyps, uterine adhesions and congenital malformations.
Tubal patency, pelvic adhesions and other pelvic abnormalities that stop the release of contrast material into the pelvis.
The blockage site may be proximal or distal. Once identified it can be corrected.
HSG should never be performed on a woman with inflamed tubes, a tender pelvic mass, or allergic to iodine.
Laparoscopy should be offered directly to women with a known contraindication to HSG.
Laparoscopy with intrauterine injection of blue dye liquid indigo carmine to confirm tubal patency is indicated for patients with abnormal findings on HSG and for patients with unexplained infertility.
If IVF is the main treatment laparoscopy may be omitted from the diagnostic workup.
Embryo implantation and IVF success is enhanced by surgical removal of the diseased tube 'hydrolsalpinx' if diagnosed by HSG or laparoscopy
Isolated proximal or distal tubal occlusions at laparoscopy may require surgery.
Combined proximal and distal occlusions are not well corrected with surgery and IVF should be recommended as the treatment of choice to achieve pregnancy in these patients.
Age is also important when deciding between tubal surgery and IVF. Older couples should be encouraged to have IVF rather than tubal surgery because the probability of their achieving a pregnancy is higher with IVF.
Cervical Factors
Abnormal cervical mucus is the recognized cause in 5% to 10% of infertile couple.
Postcoital test assesses quality of the cervical mucus and its interaction with sperm. This test is performed 24 to 48 hours before ovulation i.e on cycle day 11 to 13. The male partner must abstain from ejaculation for 48 hours before testing. The cervical mucus is examined 2 to 8 hours after intercourse. The consistency of the cervical mucus is examined and the number of motile sperm per high power field is determined.
Normal cervical mucus is acellular, clear, thin, and elastic; the mucus should stretch approximately 8 to 10 cm when placed on a glass slide and pulled. This elasticity of the cervical mucus is known as spinnbarkeit. The mucus should also contain at least 5 to 10 progressively motile sperm per high power field .
Poor Quality Cervical Mucus is thick and non-elastic. After drying on a microscope slide it has a globular rather than a fernlike pattern .
Absent or Poor Quality Cervical Mucus
Causes
Inaccurate Timing Test
Abnormality in Mucus Production as a result of Cervical Trauma or Cervical Infection
Antisperm Antibodies may cause Sperms to be both shaky and immotile on microscopic inspection. They are found in the cervical mucus of women who produce antisperm antibodies.
Lubricants or Spermicides can lead to all the sperm from a post-coital test to be immotile. The patient should be asked if she used lubricants or spermicides during intercourse.
Intrauterine insemination (IUI) bypasses the cervix and is the treatment of choice for those patients with cervical factor infertility. The procedure allows placing washed sperm directly into the endometrial cavity.
Ovulation Factors
Ovulatory dysfunction is the cause of 15% of the infertility in couples and 40% of the infertility in women.
Anovulation / absence of ovulationand and oligo / reduced frequency of ovulation account for most menstrual abnormalities.
Shortened menstrual cycles and luteal phase defects are less common causes of ovulatory dysfunction.
Ovulation Assesment.
Basal Body Temperature is the cheapest and least invasive as the patient chart her own temp daily (BBT). Correctly done the chart can aid the doctor by providing indirect evidence of ovulation. A biphasic temperature curve with elevated temperature for at least 11 to 16 days is an indication that ovulation probably occurred. The patient's own assessment of premenstrual molimina further strengthens the indirect evidence of ovulation.
Progesterone level on day 21 of the menstrual cycle provides an indirect assessment of ovulatory status. This method is less time-consuming than BBT charting.
Progesterone values of more than 15 ng/ml are consistent with ovulation.
Progesterone values of less than 5 ng/ml may indicate that ovulation has not occurred.
Progesterone values between 5 and 15 ng/ml probably indicate ovulation but give insufficient information regarding the adequacy of the
luteal phase.
Because progesterone is secreted in a pulsatile manner, only elevated values of progesterone are diagnostically useful.
In normally menstruating women 5% to 30% of all menstrual cycles involve a luteinized unruptured follicle. While ovulation symptoms and elevated progesterone levels occur during these cycles, an oocyte 'an egg' is not released and fertilization is impossible. Consequently the predictive value of indirect measures of ovulatory status is limited.
An endometrial biopsy can be performed on cycle days 23 to 26. This test can assess both the ovulatory status of the patient and the adequacy of the luteal phase.
A luteal phase defect is defined as a lag in the histologic development of the endometrium by 2 or more days when compared with the cycle day of sampling. This defect in the luteal phase is presumably caused by inadequate progesterone secretion from the corpus luteum.
Treatment by administering progesterone intramuscularly or intravaginally has aimed at prolonging the luteal phase . The benefit of this approach, however, has not been established.
Anovulation
Prolactin level assesment is done at initial evaluation of patients who are thought to be anovulatory . Elevated prolactin levels have a negative feedback effect on the hypothalamus, preventing the pulsatile release of gonadotropin-releasing hormone (GnRH). This, in turn, prevents secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. Consequently, follicular development and ovulation do not occur.
Hyperprolactinemia is responsible for 15% of all ovulatory disturbances.
If prolactin level is elevated with or without galactorrhea, the thyroid-stimulating hormone (TSH) level should be measured to rule out primary or secondary hypothyroidism. If the TSH level is normal, a computed tomography CT Scan or magnetic resonance image MRI of the head should be obtained to determine whether the patient has a prolactinoma.
Medications that deplete dopamine reserves (i.e., antidepressants, antipsychotics, and other psychotropic agents) can cause hyperprolactinemia and anovulation.
If the CT or MRI findings are abnormal or reveal a pituitary adenoma, the patient should be treated with oral bromocriptine, starting at a dosage of 2.5 to 5 mg daily, or oral cabergoline, 0.25 mg twice weekly. These medications should be titrated until prolactin levels return to normal. When prolactin levels are normalized, restoration of ovulatory function should occur.
Patients with symptomatic macroadenomas may require ablative therapy with either surgery or radiation if medical therapy does not reduce the size of the tumor or if symptoms associated with the tumor persist or worsen.
Patients with hyperprolactinemia and oligomenorrhea (except those with primary and secondary hypothyroidism, who require thyroid hormone replacement) should be treated with bromocriptine only if they are bothered by symptoms (i.e., galactorrhea) or desire fertility. If a patient remains anovulatory despite treatment with bromocriptine, oral clomiphene citrate, starting at a dosage of 50 mg daily for 5 days, can be added as an adjunctive therapy to stimulate ovulation.
If, at the time of initial examination, the patient is determined to be hypoestrogenic (i.e., she has an atrophic vagina and perineum and reports hot flashes and lack of lubrication during coital activity), the clinician should obtain serum levels of FSH, LH, and estradiol (E2). These values will identify patients with hypogonadotropic hypogonadism and those with ovarian failure.
Patients with hypogonadotropic hypogonadism should be evaluated with a GnRH-stimulation test to determine whether the problem is reversible.
Special attention should be given to anovulatory women who have normal levels of estrogen and prolactin and who have signs of hyperandrogenism and virilization. In these patients, measurements should be made of dehydroepiandrosterone sulfate (DHEAS), total testosterone, 17-hydroxyprogesterone, and 8 A.M. free urine cortisol levels. These tests will help to identify patients with
polycystic ovary syndrome (PCOS)
ovarian and adrenal neoplasms
congenital adrenal hyperplasia
Cushing syndrome.
Patients with PCOS that is associated with elevated insulin or glucose levels who wish to conceive may benefit from a combined regimen of oral metformin, 850 mg twice daily, and clomiphene citrate. Studies have shown that women treated with this combination have a higher rate of ovulation than those treated with clomiphene citrate alone.
Hirsutism and acne should not be treated medically during ovulatory induction cycles.
Elevated levels of both FSH and E2 on cycle day 3 signify a decrease in ovarian reserve (i.e. a decrease in the total number of follicles present for maturation and ovulation). The diagnosis of premature ovarian failure is reserved for women who are younger than 40 years and have gonadotropin (FSH and LH) levels in the menopausal range. Depending on the incipient age of ovarian failure, a complete autoimmune profile and possibly a genetic karyotype should be considered to establish a diagnosis. Women with an autoimmune disorder are at increased risk for developing multiple organ failure and should be screened annually. These women should be counseled to consider IVF with donor eggs or adoption.
Unexplained Infertility
The incidence of unexplained infertility is estimated to be between 15% and 20%. Couples who do not receive treatment have a monthly fecundity of 3% and a cumulative 3-year pregnancy rate of 60%. However, when a couple has experienced long-standing infertility (> 3 years) and the female partner is older than 35 years, the probability of achieving a pregnancy is markedly reduced.
The treatment for couples with unexplained infertility includes induction of superovulation with either clomiphene citrate or gonadotropins and IUI or one of the assisted reproductive technologies in vitro fertilization IVF, gamete intrafallopian transfer GIFT and zygote intrafallopian transfer ZIFT.
IUI with ovulation induction using gonadotropins produces higher pregnancy rates for couples with male-factor or unexplained infertility than does either procedure performed alone.