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Mark P. Trolice, M.D., FACOG, FACS
Board Certified, Reproductive Endocrinology And Infertility
Director, Fertility C.A.R.E. & Division Director of REI at Arnold Palmer Hospital for Children and Women in Orlando.
Overview
Physiology
Etiology
Examination
Male Factor
Ovulation and Luteal Phase
Tubal and Uterine Factor
Unexplained Infertility
Conclusion
Overview
Infertility is defined as a failure to conceive after 1 year of unprotected, appropriately timed intercourse without conception. The prevalence of infertility among couples in the United States is approximately 10%-15%. Possible contributing factors include advanced maternal age due to delay in child bearing and a decrease in sexual activity with increasing length of relationship. The natural fecundity rate (the percentage of fertile couples achieving a live birth) per month is estimated at 20%-25%. Life table analysis reveals that 64% of women with primary unexplained infertility (when all standard clinical tests yield normal results) and 79% with secondary infertility (when a previous pregnancy has occurred) will conceive within 9 years. Nevertheless, the decision to institute diagnostic tests and treatment should be made on an individual basis. This article will address the basic infertility work-up.
Physiology
Conception and pregnancy are dependent on a complex interaction of physiologic, anatomic, and immunologic factors. The man requires normal spermatogenesis, reproductive anatomy, and sexual function to provide an adequate number of morphologically normal, motile spermatozoa in the upper vagina of a woman. The woman requires a functionally intact hypothalamic-pituitary-ovarian axis to orchestrate the menstrual cycle and stimulate normal folliculogenesis, ovulation, and a luteal-phase hormonal environment. In order for the egg and sperm to meet in the fallopian tube, the sperm must initially pass through the cervical mucus, which may be impervious, depending on the time of the female's menstrual cycle. The tube must then be mobile and functional to retrieve the egg. Once fertilized, the "pre-embryo" travels to the uterus where successful implantation is contingent on an adequate hormonally stimulated endometrium, which is maintained by progesterone production from the corpus luteum. A disruption in any of these steps can result in infertility.
Etiology
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In 20%-25% of couples, both the man and woman have reproductive abnormalities. Both female and male factors each account for 40% of fertility problems.
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In 20%-25% of couples, both the man and woman have reproductive abnormalities. Both female and male factors each account for 40% of fertility problems. Other etiologic factors have been studied. Exercise programs can be associated with menstrual disturbances and decreased fertility. Strenuous activity can result in amenorrhea or oligomenorrhea by causing adverse effects on gonadotropins, androgens, estrogens, and progesterone. Cigarette smoking has been shown to affect fertility rates in an inverse ratio; some studies have shown a possible alteration in tubal physiology, transport, and cervical mucus as a result of smoking. Sperm parameters, as shown by semen analysis, have also been adversely affected by cigarette smoking.
Examination
The basic infertility work-up begins with obtaining a comprehensive medical history from both partners. In addition to the usual gynecologic history, it is important to discuss coital frequency and timing, sexual dysfunction, and use of spermicidal lubricants. Other areas of importance are endocrinologic abnormalities including galactorrhea, weight changes, acne, frontal balding, and hirsutism. The man should also give a fertility and sexual history. Also, environmental exposures may lead to an underlying cause. The woman should undergo a thorough physical examination, including a pelvic examination with cultures of Chlamydia, gonorrhea, and, possibly, mycoplasma and urea plasma, as indicated. If the semen analysis reveals abnormalities, the man's external genitalia should also be examined to exclude serious pathology. The couple's medical records of diagnostic tests should then be reviewed. It is important to provide appropriate education to assist the infertile patient or couple in the understanding of the problem, evaluation, and treatment proposed. Laboratory testing and procedures will address the etiologic factors.
Male Factor
The male factor is estimated to be significant in 40%-50% of couples. To determine the adequacy of the spermatozoa, the man must submit a semen sample for analysis after at least 2, but no more than 5 days of sexual abstinence. Sperm morphology http://myfertilitycare.com/Diagnosis/men.asp has shown to be the most important semen parameter in predicting fertility rates and pregnancy outcome in assisted reproduction. Abnormal semen parameters can result from fluctuations in hormonal levels, from genetic or congenital abnormalities, and from drug use, infections, previous surgery, and exposure to occupational and environmental toxins. Read Azospermia - Advances in Fertility Options (file: prof_azosperm) to learn more about new options for male factor infertility.
Ovulation and Luteal Phase
Ovulatory dysfunction occurs in approximately 30% of infertile patients. Presumptive evidence of ovulation is determined by using the basal body temperature (BBT) chart, steroid or gonadotropin hormone assays, and ultrasound; by analyzing cervical mucus changes; or by an endometrial biopsy. A history of regular monthly menses, premenstrual molimina, and dysmenorrhea are usually indicative of ovulation. The mid-cycle luteinizing hormone (LH) surge is the most reliable predictor or ovulation, but its analysis requires frequent blood sampling and expensive radioimmunoassay.
The determination of BBT is the oldest and most widely used test, but it is not the most accurate or reliable method of ovulation detection. Temperature elevation is secondary to the effect of progesterone on the hypothalamus. A temperature greater than 98 degrees Fahrenheit with a rise of 0.4-0.6 degrees Fahrenheit between 2 consecutive days is characteristic of ovulation. The BBT predicts the LH surge within 2-3 days. A sustained elevation of temperature for less than 10 days suggests a luteal phase deficieny (LPD). A single serum progesterone reading of greater than 3 ng/mL in the luteal phase is presumptive evidence of ovulation, and greater than 10 ng/mL virtually excludes a LPD.
The endometrial biopsy is another method of confirming ovulation but also evaluates the adequacy of the luteal phase. This test is the histologic means to diagnose a luteal-phase defect (LPD), however the clinical significance of LPD is highly dubious. More recently, the lack of alpha v beta 3 integrin expressed by the endometrium has been associated with a decreased rate of implantation. This protein is only expressed during the window of implantation and its absence is found in 50% of patients with endometriosis.
Tubal and Uterine Factor
Tubal factor infertility, a cause in 30%-50% of cases, may first be suspected on the basis of the patient's history. Significant risk factors include a history of acute salpingitis (often referred to as pelvic inflammatory disease [PID]), septic abortion, ruptured appendix, pelvic or tubal surgery, a history of an ectopic pregnancy, and possibly use of an intrauterine device. The incidence of infertility after salpingitis is 11%-12%, 23%, and 54% for one, two, and, at least, three episodes, respectively.
In addition, salpingitis increases the risk for ectopic pregnancy due to damage of the tubal mucosa. Nevertheless, about half of the patients with tubal disease or pelvic adhesions have a negative history for PID. Hydrosalpinges have been demonstrated to have a deleterious effect on implantation either from retrograde toxic fluid or absence of integrin. Salpingectomy (removing the tube) or salpingostomy (opening the tube) has been recommended to improve pregnancy rates naturally or with assisted reproduction.
The uterine factor is a rare cause of infertility, accounting for only about 2% of cases. Anatomic causes such as leiomyomas, polyps or, rarely, adhesions can impair sperm transport or embryo implantation.
Hysterosalpingography (HSG) allows the diagnosis of uterine and tubal factors. By using water soluble or oil contrast media, HSG can lead to identification of intrauterine anomalies and tubal patency. It has approximately a 75% correlation with laparoscopy and hysteroscopy for accuracy. The procedure is usually performed in the follicular phase of the menstrual cycle, 2 to 5 days after cessation of menses. The risk of infection from the procedure is less than 1% in a low-risk population and greater than 3% in a high-risk group.
Hysteroscopy and laparoscopy are the final diagnostic procedures in the basic infertility work up. Hysteroscopy can lead to identification of intrauterine adhesions, submucosal leiomyomas, and endometrial polyps. While viewing the pelvis, a laparoscopy can lead to a diagnosis of adhesions, endometriosis, or tubal disease. These procedures not only definitively diagnose uterine and pelvic factors but also facilitate operative management by the physician.
Unexplained Infertility
In addition to the heretofore outlined work up, the diagnosis of unexplained infertility may warrant further investigation. This can include bacteriologic, immunologic, sperm-penetration, and ultrasound studies. The treatment of unexplained infertility has included expectant management, controlled ovarian hyperstimulation (COH) with clomiphene citrate or gonadotropins, IUI, a combination of COH and IUI, and In-Vitro Fertilization. As with other diagnoses, treatment is ultimately determined by thorough consultation with the patient or couple after all options have been discussed.
Conclusion
A shorter duration of infertility upon initial consultation carries a more favorable prognosis. The physician should individualize treatment and be realistic. Professionals caring for patients with infertility should be aware of resources, such as RESOLVE, which offer emotional support as well as information concerning adoption. Read more about Fertility C.A.R.E.'s psychological services.
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