What’s Up With Unexplained Infertility?

Dr. Temeka Zore
Dr. Temeka Zoreover 1 year ago5 min read

Unexplained infertility is….frustrating.

Couple holding hands

To have test after test, only to be told there’s nothing wrong can feel incredibly disheartening. Because, after all, if the tests are normal then why are you struggling to conceive?!

Well, as a field of medicine, we are still figuring out the complex processes that are occurring in our bodies during ovulation, fertilization and implantation. Unfortunately, this means that we just don’t have specific tests to diagnose every condition that could be resulting in an otherwise healthy couple not being able to successfully conceive.

But there is still a lot that we do know, so let’s dive into all things unexplained infertility.

What is unexplained infertility and how common is it?

First, we should understand what infertility is defined as. Infertility is the inability to conceive after 12 months of appropriately timed intercourse. Unexplained infertility is a diagnosis of exclusion given to couples who have been trying to conceive with no success, with no obvious causes of infertility.

The standard infertility evaluation typically includes an assessment of the female partner including an understanding of ovulation status, ovarian reserve (aka numbers of follicles in the ovaries), evaluation of the uterus and fallopian tubes and a semen analysis of the male partner. Couples with this diagnosis will have regular ovulation, a normal semen analysis, a normal uterus and at least one open fallopian tube.

Surprisingly, unexplained infertility may impact up to 30% of couples trying to conceive.

What are the reasons for unexplained infertility?

If the entire evaluation is normal, couples are classified as having unexplained infertility.

And while our basic work-up may not have revealed causes of infertility there still could be underlying issues involved with reproduction that we just don’t have tests for… yet.

These may include:

  • Issues with the egg being picked up by the fallopian tube
  • Inability of sperm to successfully fertilize the egg
  • Poor embryo development
  • Problems with embryo implantation

The process of fertilization, embryo development and implantation is a complex, biological process involving multiple hormones and signal cascades to achieve a healthy embryo and normal implantation.

Often it can feel frustrating to have a diagnosis of unexplained infertility and not be able to conceive. Despite the frustration, unexplained infertility is a true diagnosis even if we can’t pinpoint the exact reason for the cause of infertility.

Unexplained infertility does NOT mean:

  • You caused your infertility
  • That it is in your head
  • That if you just relax you will conceive
  • That it is not real

Remember that.

How to get pregnant with unexplained infertility

The average fecundability (probability a cycle results in a pregnancy) for a couple with no infertility and the female partner is less than 34 years of age is approximately 20-25% per month. A couple diagnosed with unexplained infertility has a significantly lower probability of conceiving, usually about 2-4% per month. Treatment options for couples with unexplained infertility are aimed at improving the rate of pregnancy per month.

Doing nothing:

Once you’re diagnosed with unexplained infertility, most fertility doctors would recommend some form of treatment since the average monthly pregnancy rates are lower than we would want with continued attempts on your own without treatment. While the chances are certainly not zero, treatment can improve the 2-4% monthly rate of pregnancy.

Oral medications with IUI

This is the least invasive treatment option for couples with unexplained infertility. It involves taking an oral medication, called Clomid or clomiphene citrate, for 5 days. Clomid is a medication that blocks estrogen receptors in the brain and causes the pituitary gland to secrete higher amounts of FSH (follicle stimulating hormone) to grow 1-3 follicles in the ovaries.

Usually during these cycles you’ll be monitored by your fertility clinic with vaginal ultrasounds to determine how many follicles are growing and to time an insemination when your follicles reach an ideal size. A large study compared different medications combined with IUI and found that oral medications (clomid or letrozole) and IUI resulted in comparable live birth rates per cycle while minimizing twins and higher order multiples as compared to injectable medications and IUI.

It’s important to note that studies have demonstrated that clomid or letrozole with timed intercourse or natural cycle IUI alone in couples with unexplained infertility have not been shown to significantly increase the monthly chance of pregnancy and thus are not recommended first line options to treat unexplained infertility.


IVF or in-vitro fertilization involves taking injectable medications to stimulate your ovaries to develop multiple follicles. This leads to an egg retrieval and fertilization of those eggs with sperm, and subsequent embryo growth occurring outside of the body.

IVF may be recommended in couples who do not achieve a pregnancy after 3-6 attempts of medicated IUI cycles. It may also be the initial recommendation in couples where the female partner is over the age of 38 as time to pregnancy may be shortened and chance of pregnancy increased compared to starting with medicated IUI cycles.

Deciding which treatment path is right for you should be a decision you and your partner make with your physician based on your individual history, age and number of desired children.

It’s very common to feel stressed, frustrated or sad regarding the diagnosis of infertility, and even more so when it’s unexplained. It’s important that while you’re on this journey, you take care of your mental and emotional wellbeing too. You’ve got this.

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