Infertility is a disease defined by the inability to achieve a pregnancy and/or the need for medical intervention to achieve a successful pregnancy. In patients who have not achieved a pregnancy after having regular, unprotected sexual intercourse, evaluation should be initiated at 12 months if the female partner is < 35 years old and at 6 months if the female partner is ≥ 35 years.
Infertility is defined by the American Society of Reproductive Medicine (ASRM; see Definition of Infertility: A Committee Opinion [2023]) as a disease, condition, or status characterized by any of the following:
The inability to achieve a successful pregnancy based on a patient’s medical, sexual, and reproductive history, age, physical findings, diagnostic testing, or any combination of those factors.
The need for medical intervention, including, but not limited to, the use of donor gametes or donor embryos in order to achieve a successful pregnancy either as an individual or with a partner.
In patients having regular, unprotected intercourse and without any known etiology for either partner suggestive of impaired reproductive ability, evaluation should be initiated at 12 months when the female partner is < 35 years old and at 6 months when the female partner is ≥ 35 years.
Frequent, unprotected intercourse results in conception for approximately 70% of couples within 3 months, for 80% within 6 months, and for 90% within 1 year (1).
Infertility is caused by one or more factors, with the following approximate prevalences (2, 3):
Sperm disorders (24 to 35%)
Ovulatory dysfunction (21 to 25%)
Diminished ovarian reserve (increases with age)
Endometriosis (6 to 40%)
Tubal infertility (11 to 67%)
Uterine or other pelvic abnormalities (≥ 2%) (4)
Unexplained infertility (15 to 28%)
Inability to conceive often leads to feelings of anxiety, sadness, frustration, anger, guilt, resentment, and inadequacy.
Couples wishing to conceive are encouraged to have frequent intercourse when conception is most likely—during the 6 days, and particularly the 3 days, before ovulation. Ovulation is most likely to occur about 14 days before the onset of the next menstrual period.
Measuring morning basal body temperature (BBT) daily can help determine when ovulation is occurring in women with regular menstrual cycles. A decrease suggests impending ovulation; an increase of ≥ 0.5° C suggests ovulation has just occurred. However, commercially available luteinizing hormone (LH) prediction test kits, which identify the midcycle LH surge, are probably the best way for women to determine when ovulation occurs and are less time-consuming than measuring BBT. BBT can be useful if women cannot afford or do not have access to LH prediction kits. There is no evidence that any test determining when ovulation occurs improves the likelihood of pregnancy in couples having regular intercourse.
Evidence that men > 45 are less fertile than younger men, regardless of their female partner's age, is increasing.
Although infertility does not encompass recurrent pregnancy loss, the consequences are the same.
General references
1. Gnoth C, Godehardt D, Godehardt E, Frank-Herrmann P, Freundl G: Time to pregnancy: results of the German prospective study and impact on the management of infertility. Hum Reprod 18(9):1959-1966, 2003. doi:10.1093/humrep/deg366
2. Hull MG, Glazener CM, Kelly NJ, et al. Population study of causes, treatment, and outcome of infertility. Br Med J (Clin Res Ed). 1985;291(6510):1693-1697. doi:10.1136/bmj.291.6510.1693
3. Carson SA, Kallen AN. Diagnosis and Management of Infertility: A Review. JAMA. 2021;326(1):65-76. doi:10.1001/jama.2021.4788
4. Donnez J, Jadoul P. What are the implications of myomas on fertility? A need for a debate?. Hum Reprod. 2002;17(6):1424-1430. doi:10.1093/humrep/17.6.1424
Evaluation of Infertility
Tests depending on the suspected cause
If attempts to achieve pregnancy do not result in pregnancy after ≥ 1 year, both partners are evaluated. Evaluation begins with history, examination, and counseling. Men are evaluated for sperm disorders, and women are evaluated for ovulatory and tubal dysfunction and pelvic pathology.
Evaluation is done sooner than 1 year if
The woman is > 35 years old.
The woman is known to have diminished ovarian reserve (eg, because she has only one ovary).
The woman has infrequent menses.
The woman has a known abnormality of the uterus, fallopian tubes, or ovaries.
The man is known to be subfertile or is at risk of subfertility.
Tests are done depending on the suspected cause (eg, for diminished ovarian reserve, measurement of follicle-stimulating hormone and antimüllerian hormone and antral follicle count, determined by transvaginal ultrasonography; for sperm disorders, semen analysis).
Treatment of Infertility
Treatment of the primary cause
Sometimes medications to induce ovulation or spermatogenesis
Sometimes assisted reproductive technologies
The primary cause of male or female infertility is treated, if possible. For example, structural abnormalities of the reproductive tract (eg, testicular varicocele, uterine leiomyomas) or endocrine abnormalities (eg, pituitary adenoma, thyroid disorders) can be treated. Patients should be encouraged to make changes to minimize modifiable risk factors. For example, smoking cessation for people who smoke, weight loss for patients with overweight, no or moderate consumption of alcohol, and consumption of a balanced diet (with vitamins if needed) are recommended.
In general, treatment is directed at improving the likelihood of conception by increasing the availability of high-quality oocytes (eg, ovulation induction, egg donation) or sperm (eg, gonadotropin medications to induce spermatogenesis, sperm donation) and by using procedures to assist contact between the oocyte and sperm to achieve fertilization (eg, intrauterine insemination, in vitro fertilization).
People with infertility may experience sadness, anxiety, frustration, emotional stress, feelings of inadequacy, guilt, or anger. These feelings can lead to sleep or eating disturbances or clinical anxiety or depression. Counseling and behavioral health support should be offered if needed.
Giving both partners information about the treatment process is helpful. Such information includes
What the chances of success are
What the process involves, including time and costs
When to end treatment
When to consider adoption
Support groups for infertile people (eg, Family Equality, RESOLVE) may help. Clinicians should discuss adoption if the likelihood of conceiving is low (usually confirmed after 3 years of infertility, even in women < 35, or after 2 years of treatment).
More Information
The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
Family Equality: Information about becoming pregnant, (including costs) and about adoption, parenting, and legal issues pertaining to the LGBTQ community
RESOLVE: The National Infertility Association: General information about infertility, possible treatments and solutions (such as adopting or using a surrogate), and financial issues, as well as links to support groups, ways to manage stress, advice for friends and family, and resources to help LGBTQ+ people have children
World Health Organization (WHO): Infertility: Information about the definition of infertility and estimated global prevalence rates
