Infertility: Clinical sciences

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Introduction0:00–0:24

Infertility is defined as the inability to become pregnant after 12 months of timed, unprotected intercourse or donor insemination when the biologically female partner is under 35 years of age; or after 6 months when they’re older than 35.
When evaluating a patient with a chief concern suggesting infertility your first step is to obtain a focused history and physical.

Evaluation for infertility0:24–3:40

Key history findings include intercourse for 6 to 12 months that is regular, timed, and unprotected without pregnancy; history of previous infertility treatment; irregular menses; history of STIs, such as cervical infections with gonorrhea or chlamydia; pelvic infection such as pelvic inflammatory disease, or PID; galactorrhea; and hirsutism.
Additionally, when taking a history you should consider their prior pregnancies and birth control, presence of sexual dysfunction, family history of birth defects, developmental delay or early menopause, substance use including tobacco and alcohol; and occupational exposure to environmental hazards.
You should also ask about important information like surgical history, focusing on prior surgeries involving the pelvis, previous serious illness or hospitalization, and current medications including supplements.
Here’s a clinical pearl! Timed intercourse means having unprotected intercourse during the most fertile time of the menstrual cycle or “fertile window”.
This is during the 3 to 5 days leading up to ovulation. So if your patient has a 28-day cycle, you can predict they ovulate on day 14 and thus calculate their fertile window as days 10 through 14, with day 1 of their cycle being the first day of their period.Alright, if you found any of the key findings in history, you should suspect infertility and see if your patient meets the criteria for infertility.
Now, if your patient is less than 35 years old and has not become pregnant after 12 months of regular, timed, unprotected intercourse or donor insemination, or if they are at least 35 years old and have not become pregnant after 6 months, you can diagnose infertility.
The next step is to perform a basic infertility evaluation. That being said, if your patient doesn’t fit these criteria, but has at least one identifiable infertility factor, they still qualify for a basic infertility workup.
The first infertility factor is the age of 40 years or more. This is important because oocyte quantity and quality decline over time.
Next up, there is infrequent menstrual bleeding, or amenorrhea, meaning no menstrual bleeding for 3 months in individuals with previously regular cycles or 6 months in those with previously irregular cycles.
Then, known or suspected uterine, tubal, or peritoneal disease might also be present from previous infections, such as PID, or prior surgeries involving the pelvis.
Another important factor is stage 3 or 4 endometriosis, which can cause inflammation and scarring that alter pelvic anatomy.
Finally, there might be known or suspected male factor infertility.Okay, let’s discuss the basic infertility workup. The four main categories are testing for male factor infertility; ovulatory function; structural abnormalities; and ovarian reserve.Alright, male factor infertility can cause up to half of infertility in heterosexual couples, so it is really important to test this along with female factors.

Basic infertility workup3:40–6:56

Male factor testing is completed by obtaining a semen analysis. Next, testing ovulatory function includes assessing for regular, monthly ovulation, which is a good sign if present.
However, specific testing for ovulation may be completed, which includes a midluteal serum progesterone that rises after ovulation, or home ovulation predictor kits.
These kits test the urine for a surge in the luteinizing hormone, or LH, that occurs about 24 hours prior to ovulation. Next up, structural abnormalities, also known as tubal or uterine factors, include tubal occlusion; peritubal adhesions; endometrial polyps; submucosal fibroids, which can distort the endometrial cavity; and uterine synechiae, such as adhesions.
Testing can include a hysterosalpingogram, which is done by injecting radiopaque dye through the cervix into the uterus while using fluoroscopy to determine tubal patency.
Another test you can do is a transvaginal ultrasound with or without 3D imaging. This is often more readily available than other options and can evaluate for uterine fibroids and some Mullerian anomalies.
The benefits include being able to evaluate the adnexa as well. Limitations include difficulty differentiating submucosal fibroids from endometrial polyps.
Sonohysterogram is another option that’s performed by injecting saline through the cervix into the uterus during a transvaginal ultrasound.
The saline distends the endometrial cavity and provides contrast to evaluate the endometrium. This is a great tool to check for uterine factors.
A combination of air and saline can also be injected, called the “bubble test”, in which bubbles are followed from the cornua through the fallopian tubes to evaluate tubal patency.
Finally, there’s hysteroscopy, or using a camera to visualize the endometrial cavity. It’s the most direct way to visualize and treat endometrial pathology, but is often not the first line due to cost and access.Finally, ovarian reserve represents the number of available oocytes.
Typically, testing is done by either checking anti-mullerian hormone, or AMH, or follicle stimulating hormone, known as FSH, and estrogen on cycle days 2 to 5.
You can also obtain a transvaginal ultrasound with an antral follicle count, but this is a relatively poor predictor for the ability to get pregnant in the future.
First, let’s review male factor infertility, which requires semen analysis. Results that indicate an abnormal test include low total sperm, low motility, and/or abnormal morphology.

Male factor infertility6:56–7:22

If any of these are found, male factor infertility is diagnosed and further evaluation with an urology consultation is indicated.Next up, check for ovulatory dysfunction.

Ovulatory dysfunction7:22–8:47

Now, the infertility workup might reveal abnormal ovulatory function, in which case the patient's midluteal progesterone is low, indicating ovulation did not occur, or if they have negative home ovulation predictor kits.
In this scenario, you can diagnose ovulatory dysfunction. This accounts for a significant portion of female infertility and may be related to obesity, hypothalamic and pituitary dysfunction, PCOS, and other conditions.
Next, check an hCG to rule out pregnancy, a thyroid-stimulating hormone to evaluate thyroid function, and a prolactin level to screen for hyperprolactinemia.
Once you get the results, treat the underlying condition and recheck ovulatory function thereafter. Here’s a clinical pearl!
In many cases, menstrual history can be enough to assess ovulatory dysfunction. Clinical history can be used to assess ovulatory cycles, as most ovulatory patients will have regular menstrual cycles preceded by premenstrual symptoms.
However, keep in mind that up to one third of patients with normal menstrual cycles are anovulatory. Hence, confirming ovulation should be considered for a comprehensive assessment.Another possibility of infertility workup is structural abnormality.

Structural abnormality8:47–9:20

It’s possible to find evidence of a uterine cavity lesion, such as an endometrial polyp, submucosal fibroid, or uterine synechiae during your evaluation.
These can all impact fertility by affecting the endometrium leading to issues with implantation. If you find any of these, diagnose a structural abnormality.
Treatment is typically performed with operative hysteroscopy to remove the lesion. Okay, let’s talk about another important finding, which is an abnormal ovarian reserve.

Abnormal ovarian reserve 9:20–10:30

Now, ovarian reserve testing interpretation is not quite as clear-cut as some of our other tests. If you find low AMH or antral follicle counts, or high FSH, diagnose abnormal ovarian reserve.
Management is a bit more complex because while these labs indicate a poor response to ovarian stimulation, they do not correlate with live birth rates.
Recommendations include having the patient continue to attempt pregnancy and seek further evaluation with a reproductive endocrinologist and infertility, or REI, specialist.
Here’s another clinical pearl! A normal AMH also does not predict live birth rates!
Instead, a normal AMH is a good predictor of response to ovarian stimulation, such as with in vitro fertilization. It has no correlation with those attempting to conceive without ovarian stimulation and should be used with caution when reassuring patients of their fertility status.
Finally, it’s important to know what to do if all the testing is normal. When this occurs, your patient falls into the category of unexplained infertility which is diagnosed in almost a third of couples!

Unexplained infertility10:30–11:02

The recommendation is ovulation induction with oral medications, such as clomiphene or letrozole, along with timed intrauterine insemination, or IUI.
Consideration for further evaluation with a REI provider is also encouraged.Okay, let’s go all the way back to assessing infertility criteria, and talk about patients that do not meet these criteria and have no identifiable infertility factors.

Does not meet criteria11:02–11:35

In this case, they should continue to attempt pregnancy. Counsel them on intercourse timing to ensure they are aware of their fertile window.
If they have chronic health conditions, work on optimizing their health prior to pregnancy. Lastly, be sure to tell them to return if they ultimately meet the criteria for infertility.
Alright, as a quick recap… Infertility is defined as the inability to conceive after 12 months of timed, unprotected intercourse or donor insemination for biologically female patients younger than 35 years old or 6 months for those 35 years and older.

Review11:35–12:26

A basic infertility workup includes testing for male factor infertility, ovulatory dysfunction, evaluating for tubal or uterine structural abnormalities, and abnormal ovarian reserve.
Treatment is based on your findings. Your patient might need management of underlying conditions such as PCOS and hypothalamic dysfunction; hysteroscopy to remove uterine cavity lesions; urology evaluation for abnormal semen analysis; ovulation induction with IUI; or further evaluation with a REI provider.