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Overview of infertility
Authors: Wendy Kuohung, MD, Mark D Hornstein, MD
Section Editor: Robert L Barbieri, MD
Deputy Editor: Kristen Eckler, MD, FACOG

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Feb 2023. | This topic last updated: Feb 15, 2023.

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.

This topic review will provide an overview of infertility issues. More detailed
discussions of both male and female infertility are found elsewhere.

● Female-specific content

• (See "Female infertility: Causes".)

• (See "Female infertility: Evaluation".)

• (See "Female infertility: Treatments".)

● Male-specific content

• (See "Causes of male infertility".)

 • (See "Approach to the male with infertility".)

• (See "Treatments for male infertility".)

In this topic, when discussing study results, we will use the terms "woman/en",
"man/en", or "patient(s)" as they are used in the studies presented. However, we
encourage the reader to consider the specific counseling and treatment needs of
transgender and gender-expansive individuals.

DESCRIPTION AND RELATED TERMS

The American Society for Reproductive Medicine (ASRM) description of infertility

includes [1,2]:

● It is a "disease historically defined by the failure to achieve a successful

pregnancy after 12 months or more of regular, unprotected sexual intercourse
or due to an impairment of a person's capacity to reproduce either as an
individual or with her/his partner."

● The disease generates disability through impairment of function.

● Further, "in the absence of exigent history or physical findings, evaluation

should and treatment may be initiated at 12 months in women <35 years of
age and at six months in women aged ≥35 years. In women >40 years of age,
more immediate evaluation and treatment may be warranted.

Other terms used when discussing fertility include [3]:

● Fecundity is clinically defined as the capacity to have a live birth.

● Fecundability is the probability of achieving a pregnancy in a single menstrual

cycle with adequate sperm exposure and no contraception that results in a live
birth.

● Fertility is the ability to have a clinical pregnancy.

● Sterility is a permanent state of infertility.

 ● Time to pregnancy refers to the length of time, usually measured in months,
that it takes a couple to conceive. This parameter is often used in
epidemiological studies as a measure of subfecundity [4,5].

NORMAL FERTILITY

Most pregnancies occur during the first six menstrual cycles of attempted
conception [5-9]. Additional details of normal fertility are presented in related
content. (See "Natural fertility and impact of lifestyle factors", section on 'What is
normal natural fertility?'.)

FACTORS INFLUENCING PREVALENCE

The prevalence of infertility varies based on the definition used and study variables
included, such as time/period, geographic region, and patient demographic factors.

● Impact of increasing female age – Infertility prevalence generally rises with

increasing female age. Analysis of data from the 2016 Global Burden of
Disease Study reported females aged 20 to 24 years had the lowest rates of
infertility (approximately 3 percent) while those aged 35 to 39 years had the
highest rates (approximately 5.5 percent) [10]. Age-specific contributors
include declining ovarian reserve and accrued impact of gynecologic disease,
medical comorbidities, and infection, among others. (See "Evaluation and
management of infertility in females of advancing age".)

● Impact of race/ethnicity – While race/ethnicity may impact the prevalence of

infertility [11], this association likely reflects underlying confounders, such as
socioeconomic disadvantage, rather than a true relationship [12].

● Impact of nulliparity – For females, nulliparous individuals are more likely to

experience infertility than those with a prior pregnancy, across all age groups.
In the analysis of data from the US National Survey of Family Growth,
nulliparous individuals as a group had more than twice the prevalence of
infertility compared with parous individuals (13 versus 6 percent) [11].
Nulliparous individuals aged 35 to 39 years had a nearly fourfold increased
 prevalence of infertility compared with their parous counterparts (27.2 versus
7 percent).

● Access to reproductive health services – The ability to access reproductive

health services is associated with reduced prevalence of infertility, likely
through improved screening and treating of gynecologic disease and infection
[11]. This finding has significant implications for public policy.

CAUSES OF INFERTILITY

The World Health Organization (WHO) task force on Diagnosis and Treatment of
Infertility performed a study of 8500 infertile couples and utilized standard
diagnostic criteria to determine the medical conditions contributing to infertility
[13]. 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, 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 oligomenorrhea 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 [14]:

● 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 [15].

These causes are discussed in detail separately:

● (See "Female infertility: Causes".)

● (See "Causes of male infertility".)

WHO SHOULD PERFORM THE INFERTILITY EVALUATION?

Infertility evaluations should be directed by fertility specialists or physicians with

experience in the evaluation and treatment of infertility, where available. In many
cases, it is appropriate for primary care physicians to initiate portions of the
infertility evaluation. In general, obstetricians-gynecologists should be 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 [16-21]. Although a less experienced provider may initiate the
infertility evaluation, couples with abnormal test results should be referred to a
specialist.

Specific guidelines for practices offering assisted reproductive technologies have

been developed by the American Society for Reproductive Medicine [22].

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, but earlier evaluation should be undertaken
based on medical history and physical findings, and in women over 35 years of age
( table 1) [23]. Some authorities have proposed initiating an infertility work-up
after six months of fertility-oriented intercourse without conception since
prospective cohort studies have shown that a significant decline in fecundity occurs
by this time [5,8,24].

The timing of initial evaluation of infertility depends upon the age of the female
partner, as well as the couple's historical risk factors ( table 2). Women experience
a decline in fecundity as the ovary ages, especially after age 30 [25]. 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 [23].

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 [26]. 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. (See "Natural fertility and impact of lifestyle factors".)

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. (See "Psychological stress
and infertility".)

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 [26]. 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 3 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.

A detailed description of the approach to evaluation of the male and female

partners can be found separately:

● (See "Female infertility: Evaluation".)

● (See "Approach to the male with infertility".)

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). (See "Natural fertility and
impact of lifestyle factors".)

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 [27-29].
The parent's marital status, sexual orientation, and HIV status should not be used to
deny infertility treatment [30,31].

Approaches to treatment of the male and female partners are described in detail
separately:

● (See "Female infertility: Treatments".)

● (See "Treatments for male infertility".)

● (See "Unexplained infertility".)

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 low birth weight, preterm birth, and severe maternal
morbidity [32-37]. Compared with the general population, however, an increased
risk of preterm birth and low birth weight has also been observed among untreated
subfertile women who conceived naturally [35,38]. 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.
(See "Assisted reproductive technology: Pregnancy and maternal outcomes".)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and

regions around the world are provided separately. (See "Society guideline links:
Female infertility".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond
the Basics." The Basics patient education pieces are written in plain language, at the
5th to 6th grade reading level, and they answer the four or five key questions a
patient might have about a given condition. These articles are best for patients who
want a general overview and who prefer short, easy-to-read materials. Beyond the
Basics patient education pieces are longer, more sophisticated, and more detailed.
These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical
jargon.

Here are the patient education articles that are relevant to this topic. We encourage
you to print or e-mail these topics to your patients. (You can also locate patient
education articles on a variety of subjects by searching on "patient info" and the
keyword(s) of interest.)

● Basics topics (see "Patient education: Infertility in couples (The Basics)")

● Beyond the Basics topics (see "Patient education: Evaluation of infertility in

couples (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

● Definition and timing of evaluation – Infertility is classically defined as the

failure of a couple to conceive; the time frame varies with the age of the female
partner ( table 1). Fecundability is the probability of achieving a pregnancy in
one menstrual cycle. (See 'Description and related terms' above.)

• For persons under age 35 years, infertility is the lack of conception after 12
months of regular and appropriately timed intercourse without use of
contraception. (See 'Timing of infertility evaluation' above.)
 • For persons age 35 years and older, infertility is the lack of conception after
six months of regular and appropriately timed intercourse without use of
contraception. (See 'Timing of infertility evaluation' above.)

• Earlier evaluation may be justified based on medical history (eg, history of

chemotherapy or pelvic radiation) and physical findings (eg, pelvic mass).

● Fecundability – While 80 to 90 percent of couples (combined data, all age

groups) will conceive within 12 months of attempting pregnancy, fecundability
progressively decreases over time. (See 'Normal fertility' above.)

● Common identifiable causes – Infertility can be due to female factors, male

factors, or factors contributed by both partners. (See 'Causes of infertility'
above.)

• Female-specific factors include ovulatory dysfunction, tubal damage,

endometriosis, and cervical factor.

• Male-specific factors include hypogonadism, post-testicular defects, and

seminiferous tubule dysfunction.

• Other causes – In some cases, infertility is due to coital problems or is

unexplained. (See "Unexplained infertility".)

● Evaluation – Components of the basic infertility evaluation include history

( table 2) and physical examination, semen analysis, menstrual history,
laboratory tests, and assessment of the fallopian tubes and uterus using
hysterosalpingography, hysteroscopy, ultrasonography, and/or laparoscopy.
Common laboratory tests include assessment of ovarian reserve (may include
day 3 serum follicle-stimulating hormone and estradiol levels, anti-müllerian
hormone, and/or antral follicle count) and thyroid-stimulating hormone level.
(See 'Infertility evaluation' above.)

● Treatment – If a 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. (See 'Treatment' above.)
 Discussion of targeted treatments, as well as discussion of unexplained
infertility, are described in detail separately.

• (See "Female infertility: Treatments".)

• (See "Treatments for male infertility".)

• (See "Unexplained infertility".)

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Topic 7396 Version 42.0

GRAPHICS

Indications and timing of the infertility evaluation

Infertility evaluation is indicated for couples who seek help because they
have not been able to conceive.

1. Initiate evaluation after 12 months of unprotected and frequent

intercourse:

Women under age 35 years without risk factors for infertility

2. Initiate evaluation after six months of unprotected and frequent

intercourse:
Women age 35 to 40 years

3. Initiate evaluation upon presentation despite less than six months of

unprotected and frequent intercourse:

Women over age 40 years

Women with oligomenorrhea/amenorrhea

Women with a history of chemotherapy, radiation therapy, or advanced stage

endometriosis

Women with known or suspected uterine/tubal disease

Women whose male partner has a history of groin or testicular surgery, adult
mumps, impotence or other sexual dysfunction, chemotherapy and/or radiation,
or a history of subfertility with another partner

Graphic 70415 Version 5.0

Infertility evaluation: History

Male Female

Duration of infertility Duration of infertility

Fertility in other Number and outcome of any prior pregnancies (including

relationships ectopic and miscarriages) with the same or a different partner

Medical and surgical Gynecologic history, including history of pelvic inflammatory

history, including disease, fibroids, endometriosis, cervical dysplasia; surgery of
testicular surgery the cervix, ovary, uterus, fallopian tube, pelvis, or abdomen;
and history of intrauterine device use, other prior contraceptive use,
mumps diethylstilbestrol exposure in utero, uterine anomalies.

Menstrual history (age at menarche, cycle length, and

regularity), presence of molimina or vasomotor symptoms (hot
flashes), dysmenorrhea

Changes in hair growth, body weight, or breast discharge

Other medical and surgical history

Medications Medications

History of History of chemotherapy or radiation

chemotherapy or
radiation

Cigarette smoking, Cigarette smoking, alcohol, marijuana and other drug use;
alcohol, marijuana environmental and occupational exposures
and other drug use;
environmental and
occupational
exposures

Sexual dysfunction Exercise and dietary history

or impotence

Frequency of Frequency of intercourse, use of lubricants (which may be toxic

intercourse, use of to sperm). Presence of deep dyspareunia suggestive of
lubricants (which endometriosis.
may be toxic to
sperm)

Previous infertility Previous infertility testing and therapies

testing and therapies

Family history of Family history of birth defects, intellectual disability, or

 birth defects, reproductive failure
intellectual disability,
or reproductive
failure

  Pelvic or abdominal pain, symptoms of thyroid disease

Graphic 50278 Version 5.0