INTRODUCTION
Infertility is a common condition with important psychologic, economic, demographic, and medical implications. Demand for infertility services has grown substantially, even though the prevalence of infertility has been stable. This phenomenon may be due to entry of the “baby boom” generation into the reproductive age group during a period of highly publicized technologic advances and unparalleled publicity given to fertility issues in the lay press.
DEFINITIONS
Infertility is a unique medical condition because it involves a couple, rather than a single individual. It is defined as inability of a couple to conceive after 12 months of regular intercourse without use of contraception in women less than 35 years of age; and after six months of regular intercourse without use of contraception in women 35 years and older. Some clinicians use the term subfertility to describe this failure to conceive unless the couple has been proven to be sterile.
Fecundability, the probability of achieving a pregnancy in one menstrual cycle, is a more accurate descriptor because it recognizes varying degrees of infertility.
NORMAL FERTILITY
The concept of fecundability has proven useful for establishing normal parameters in studies of fertility potential:
- A study examined the number of months to conception in 5,574 normal women who had unprotected intercourse and who became pregnant between 1946 and 1956. Within 12 months, 85 percent of the women conceived. Fecundability was 0.25 in the first three months of observation, and then decreased to 0.15 during the next nine months of observation.
- Another study of 200 healthy couples who desired pregnancy also noted that fecundability declined from 25 percent in the first three months to 0.11 in the next nine months of observation. Within 12 months, 82 percent of the couples conceived.
- A study conducted in China reported that 518 newly married textile workers aged 20 to 34 years who intended to conceive did so at a rate of about 50 percent within two cycles and 88 percent within six months. Monthly fecundity ranged from 0.30 to 0.35.
- A prospective European study investigated 346 users of natural family planning methods who were trying to achieve conception. The estimated cumulative probabilities of conception for the total group were at 1 month, 38 percent; 3 months 68 percent; 6 months, 81 percent; and 12 months, 92 percent. The authors postulated that after six months, 50 percent of the remaining couples were subfertile or infertile.
- A study of a random sample of 867 women from the general population having unprotected intercourse with a male partner reported pregnancy rates within 6 months at 54 percent; 12 months, 76 percent; and 24 months, 89 percent.
While these studies demonstrate that the large majority (80 to 90 percent) of apparently normal couples will conceive within the first year of attempted conception, they also show that the fecundability of the test group decreases over time and with increasing age of the female partner. Patients who have not achieved pregnancy after 12 months have even lower fecundability. Five to 15 percent of apparently normal couples will conceive in the second 12 months of attempted conception so that after 24 months of trying to become pregnant, 95 percent of couples will have conceived.
Several authorities have proposed a system of prognostic grading in conjunction with statements describing the couple’s fertility history and diagnosis in order to reduce confusing terminology and to facilitate an appropriate treatment plan. This system has not yet been widely accepted. In general, women who are under age 30, who have a less than two-year history of infertility, who have had a previous pregnancy, and who do not have tubal disease, anovulation, partners with male factor infertility, or endometriosis, have the best prognosis for treatment-independent conception.
PREVALENCE OF INFERTILITY
The National Survey of Family Growth (NSFG) interviewed 12,279 women aged 15 to 44 years to estimate the prevalence of infertility in the United States. A woman was considered infertile if she reported she and her husband or partner were continuously married or cohabiting during the previous 12 months or longer, were sexually active each month, had not used contraception, and had not become pregnant. The percentage of women meeting these criteria was 8.5 percent in 1982. It fell to 6.0 percent from 2006 to 2010. This figure is lower than the incidence of infertility estimated from prospective studies in the U.S., which ranges from 12 to 18 percent. It is also lower than the rate in nulliparous married women (women who have not given birth to a surviving baby), which represents primary infertility. The frequency of primary infertility in married women by age groups was: women 15 to 34 years, 7.3 to 9.1 percent; 35 to 39 years, 25 percent; 40 to 44 years, 30 percent.
The reasons for these discordant trends cannot be fully explained. However, it is clear that many women seek medical advice and intervention to help them become pregnant. In a 2002 NSFG report, 2 percent of reproductive aged women had one or more visits with a health care provider for this indication and 10 percent had received infertility services at some time in their lives. In the most recent report in 2013, 64 percent of nulliparous married women with infertility intended to have a child, as did 53 percent of parous, married, infertile women.
Worldwide, the prevalence of infertility is highest in Eastern Europe, North Africa/Middle East, Oceania, and Sub-Saharan Africa. Worldwide, in 2010, 1.9 percent of women aged 20 to 44 years who wanted to have children were unable to have their first live birth and 10.5 percent of women with a previous live birth were unable to have an additional live birth. However, definitions and survey methodology of infertility markedly vary between the U.S. and other countries. In this study, infertility was defined as “the absence of a live birth for women who desire a child and have been in a union for at least five years, during which they have not used any contraceptives.”
CAUSES OF INFERTILITY
The World Health Organization (WHO) task force on Diagnosis and Treatment of Infertility performed a study of 8,500 infertile couples and utilized standard diagnostic criteria to determine the medical conditions contributing to infertility. In developed countries, female factor infertility was reported in 37 percent of infertile couples, male factor infertility in 8 percent, and both male and female factor infertility in 35 percent. Five percent of couples had unexplained infertility and 15 percent became pregnant during the study. This study illustrates that infertility should not be assumed to result primarily from disorders in the female partner.
Some causes of infertility are easily identifiable, such as azoospermia (no sperm cells in the ejaculate), longstanding amenorrhea (abnormal absence of menstruation), or bilateral tubal obstruction. However, the situation is less clear in most couples: the sperm may be reduced in number, but are not absent; there may be infrequent menstruation with some ovulatory cycles; the woman may have partial tubal obstruction; or a menstrual history may suggest intermittent ovulation. It is often difficult to weigh or prioritize these findings when counseling infertile couples or planning treatment programs.
Adding to the complexity of the situation, there are few data regarding the predictive validity of these tests despite their widespread use. Thus, short of the absolute infertility factors mentioned (eg, azoospermia or bilateral tubal obstruction), an abnormal test result cannot be said to be the cause of infertility in a particular couple.
The uncertain causal relationship between an abnormality on infertility testing and the actual cause of infertility makes it difficult to estimate the relative frequency of the causes of infertility. Nevertheless, it is instructive to estimate the frequency with which various factors are found in association with infertility as a rough proxy for their relative importance. One population-based study reported the following results:
- Male factor (hypogonadism, post-testicular defects, seminiferous tubule dysfunction) – 26 percent
- Ovulatory dysfunction – 21 percent
- Tubal damage – 14 percent
- Endometriosis – 6 percent
- Coital problems – 6 percent
- Cervical factor – 3 percent
- Unexplained – 28 percent
Of note, the total in the above study for all causes of infertility is greater than 100 percent because some couples had more than one problem. The frequency of these factors in infertility is similar whether infertility is primary or secondary, and has not changed significantly over the past 25 years in developed countries.
WHO SHOULD PERFORM THE INFERTILITY EVALUATION?
Infertility evaluations should be directed by physicians with experience in the evaluation and treatment of infertility. In general, obstetricians-gynecologists are able to perform the basics of the fertility work-up. In observational studies, however, providers with expertise in diagnosis and treatment of infertility tended to provide more cost-effective care than less experienced primary care providers, and were generally more able to fulfill the emotional, informational, and diagnostic needs of their patients.
Specific guidelines for practices offering assisted reproductive technologies have been developed by the American Society for Reproductive Medicine.
TIMING OF INFERTILITY EVALUATION
The general consensus among infertility experts is that infertility evaluation should be undertaken for couples who have not been able to conceive after 12 months of unprotected and frequent intercourse. Earlier evaluation should be undertaken based on medical history and physical findings, and in women over 35 years of age. Some authorities have proposed initiating an infertility work-up after six months of fertility-oriented intercourse without conception since prospective group studies have shown that a significant decline in fecundity occurs by this time.
The timing of initial evaluation of infertility depends upon the age of the female partner, as well as the couple’s historical risk factors. Women experience a decline in fecundity as ovaries age, especially after age 30. Significantly delaying the evaluation and treatment of an infertile woman in her mid-thirties may diminish the success rate once therapy is initiated. For these reasons, in women between 35 and 40 years of age, we initiate the infertility evaluation after six months of frequent unprotected intercourse without conception and we initiate the evaluation after less than six months in women over 40 years of age. The American College of Obstetricians and Gynecologists (ACOG) and the American Society for Reproductive Medicine (ASRM) recommend that women older than 35 years receive an expedited infertility evaluation and undergo treatment after 6 months of failed attempts to conceive or earlier, if clinically indicated.
Evaluation is also initiated promptly if the female partner has a history of risk factors for premature ovarian failure (previous extensive ovarian surgery, exposure to cytotoxic drugs or pelvic radiation therapy, autoimmune disease, smoking, strong family history of early menopause/premature ovarian failure), advanced stage endometriosis, or known or suspected uterine/tubal disease. Male factors can also be indications for initiating early evaluation of the male partner. These factors include a history of testicular trauma requiring treatment, adult mumps, impotence or other sexual dysfunction, chemotherapy and/or radiation, or a history of subfertility with another partner.
For younger couples who present with fewer than 12 months of attempted conception, we suggest focusing the initial intervention on teaching timed intercourse, often with the aid of a urinary ovulation predictor kit, and advising that they wait at least 12 months before initiating the infertility evaluation. This recommendation may be modified to fit the specific circumstances of the couple.
In addition, we recommend changes in lifestyle factors that may improve fertility, including achieving an ideal body mass index, cessation of smoking, and limiting exposure to caffeine and alcohol. As discussed above, evaluation is initiated sooner if the female partner has a history of oligomenorrhea/amenorrhea, chemotherapy and/or radiation, or endometriosis, known or suspected tubal disease, or if male risk factors are present.
INFERTILITY EVALUATION
The recognition, evaluation, and treatment of infertility are stressful for most couples. The clinician should not ignore the couple’s emotional state, which may include depression, anger, anxiety, and marital discord.
It is important to remember that the couple may have multiple factors contributing to their infertility; therefore, a complete initial diagnostic evaluation, including a complete history and physical examination, should be performed. This will detect the most common causes of infertility, if present. Evaluation of both partners is performed concurrently. The same approach is used for both primary and secondary infertility.
The following tests are useful in most couples with infertility:
- Semen analysis to assess male factors
- Menstrual history, assessment of luteinizing hormone surge in urine prior to ovulation, and/or luteal phase progesterone level to assess ovulatory function
- Hysterosalpingogram or sonohysterogram with a test of tubal patency such as hysterosalpingo-contrast-sonography to assess tubal patency and the uterine cavity.
- Assessment of ovarian reserve with day three serum follicle-stimulating hormone and estradiol levels, anti-Müllerian hormone, and/or antral follicle count.
- Thyroid-stimulating hormone.
In select couples, the following additional tests may be warranted: - Pelvic ultrasound to assess for uterine myomas and ovarian cysts
- Laparoscopy to identify endometriosis or other pelvic pathology
TREATMENT
Once the cause of infertility is identified, therapy aimed at correcting reversible etiologies and overcoming irreversible factors can be implemented. The couple is also counseled on lifestyle modifications to improve fertility, such as smoking cessation, reducing excessive caffeine and alcohol consumption, and appropriate timing and frequency of coitus (every one to two days around the expected time of ovulation or according to an ovulation predictor kit).
Therapeutic interventions for treatment of male and female infertility may involve drug therapy, surgery, and/or procedures such as intrauterine insemination or in vitro fertilization. Further research on causes of infertility and therapeutic modalities is needed to improve the overall success of infertility treatment. Reducing the cost of therapy, the risk of multiple gestation, and complications such as ovarian hyperstimulation will improve patient acceptance of, and the safety of, infertility therapy.
The only absolute contraindications to infertility therapy are contraindication to pregnancy and contraindication to use of the drugs or surgery used to enhance fertility. The ethics of restricting infertility therapy for other reasons, such as parental child-rearing ability, severe obesity, lifestyle issues (tobacco smoking, alcohol consumption), are controversial and beyond the scope of this review. The parent’s marital status, sexual orientation, and HIV status should not be used to deny infertility treatment.
PREGNANCY OUTCOME
Women who use infertility therapies (in vitro fertilization [IVF] or non-IVF) appear to have a small but statistically significant increase in risk of some pregnancy complications, such as preterm birth. Compared to the general population, an increased risk of preterm birth and low birth weight has also been observed among untreated subfertile women who conceived naturally. The relationship between the various causes of infertility, types of infertility treatment, and pregnancy outcomes requires further study to determine the specific risks and the mechanisms involved.
SUMMARY AND RECOMMENDATIONS
- Infertility is classically defined as the failure of a couple to conceive after 12 months of frequent intercourse without use of contraception in women under age 35, and after six months in women over age 35. Fecundability is the probability of achieving a pregnancy in one menstrual cycle.
- Eighty to 90 percent of couples will conceive within 12 months of attempting pregnancy. Fecundability progressively decreases over time.
- Infertility can be due to male factors, female factors, or factors contributed by both partners. Identifiable male factors include hypogonadism, post-testicular defects, and seminiferous tubule dysfunction. Diagnosable female factors include ovulatory dysfunction, tubal damage, endometriosis, and cervical factor. In some cases, infertility is due to coital problems or is unexplained.
- The general consensus among infertility experts is that infertility evaluation should be undertaken for couples who have not been able to conceive after 12 months of unprotected and frequent intercourse, but earlier evaluation can be justified based on medical history and physical findings, and in women over 35 years of age.
- Components of the basic infertility evaluation include history and physical examination, semen analysis, menstrual history, laboratory tests, and assessment of the fallopian tubes and uterus using hysterosalpingography, hysteroscopy, ultrasonography, and/or laparoscopy.
- Once the cause of infertility is identified, therapy aimed at correcting reversible etiologies and overcoming irreversible factors can be implemented. Therapeutic interventions for treatment of male and female infertility may involve drug therapy, surgery, and/or procedures such as intrauterine insemination or in vitro fertilization.
This topic retrieved from UpToDate on: Nov 21, 2018.
