From the Guidelines
An initial infertility work-up for a couple should begin with a comprehensive medical history and physical examination for both partners, including a reproductive history and semen analysis for the male partner, as recommended by the most recent guidelines 1. The initial evaluation should include assessing menstrual history, previous pregnancies, contraceptive use, and any symptoms of endocrine disorders for the female partner.
- Laboratory tests should include measurements of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and anti-Müllerian hormone (AMH) on day 3 of the menstrual cycle to evaluate ovarian reserve.
- Thyroid function tests (TSH, free T4) and prolactin levels should be checked to rule out endocrine abnormalities.
- A transvaginal ultrasound should be performed to assess the uterus and ovaries, while a hysterosalpingogram (HSG) using contrast dye can evaluate tubal patency. For the male partner,
- a semen analysis is essential, examining parameters such as volume, concentration, motility, and morphology, as recommended by the American Urological Association (AUA) and the American Society for Reproductive Medicine (ASRM) 1.
- If abnormalities are found, further testing may include hormonal evaluation (testosterone, FSH, LH) and possibly genetic testing, as suggested by the Human Reproduction Update study 1. Both partners should be screened for sexually transmitted infections that could impact fertility. This systematic approach allows clinicians to identify the most common causes of infertility, including ovulatory disorders, tubal factors, male factors, and unexplained infertility, which together account for the majority of cases, as discussed in the Journal of the American College of Radiology study 1. Early identification of these issues enables appropriate treatment planning, whether through medication, surgical intervention, or assisted reproductive technologies. The initial evaluation for male factor infertility should include a physical examination performed by an examiner with appropriate training and expertise, a reproductive history, and at least one properly performed semen analysis, as strongly recommended by the Human Reproduction Update study 1.
From the FDA Drug Label
The workup and treatment of candidates for clomiphene citrate therapy should be supervised by physicians experienced in management of gynecologic or endocrine disorders. Patients should be chosen for therapy with clomiphene citrate only after careful diagnostic evaluation The initial steps in an infertility work-up for a couple include a careful diagnostic evaluation. This evaluation should be supervised by physicians experienced in management of gynecologic or endocrine disorders.
- The plan of therapy should be outlined in advance
- Impediments to achieving the goal of therapy must be excluded or adequately treated before beginning treatment 2
From the Research
Initial Steps in Infertility Work-up
The initial steps in an infertility work-up for a couple involve a comprehensive evaluation to identify the underlying causes of infertility. According to 3, 4, 5, 6, 7, the following are the key components of an initial work-up:
- A thorough medical history and physical examination of both partners to identify any potential risk factors or underlying medical conditions that may be contributing to infertility.
- Documentation of ovulation using a home urinary luteinizing hormone kit or serum progesterone level measurement at cycle day 21 3, 6.
- Semen analysis for the male partner to evaluate sperm quality and quantity 4, 5, 6.
- Imaging studies such as hysterosalpingography, pelvic ultrasonography, or laparoscopy to evaluate the female reproductive organs and detect any structural abnormalities or tubal disease 3, 4, 5, 6.
Evaluation of Female Partner
The evaluation of the female partner may include:
- Assessment of ovarian reserve using follicle-stimulating hormone and estradiol levels on day 3 of the menstrual cycle, the clomiphene citrate challenge test, or pelvic ultrasonography for antral follicle count 3, 4.
- Evaluation of ovulatory function using ovulation induction agents or timed intercourse 7.
- Imaging studies to detect uterine or fallopian tube disease, such as hysterosalpingography or laparoscopy 3, 4, 5, 6.
Evaluation of Male Partner
The evaluation of the male partner may include:
- Semen analysis to evaluate sperm quality and quantity 4, 5, 6.
- Medical history and physical examination to identify any underlying medical conditions that may be contributing to infertility 4, 5.
- Referral to a specialist with expertise in male reproductive medicine if necessary 4.
Unexplained Infertility
In cases of unexplained infertility, the couple may undergo further evaluation and treatment, including:
- Ovulation induction with timed intercourse or intrauterine insemination 7.
- In vitro fertilization (IVF) if other treatments are unsuccessful 7.
- Lifestyle modifications, such as limiting alcohol intake, avoiding tobacco and illicit drug use, consuming a profertility diet, and losing weight if obese, to improve pregnancy success rates 5.