Getting Pregnant With Unexplained Infertility

If you are facing unexplained infertility, you may wonder if there is an ideal way to get pregnant. While there’s no straightforward answer, typically, when you can’t get pregnant, the first step is fertility testing. Then, once a cause (or causes) is found, an appropriate treatment is pursued.

But what do you treat when your healthcare provider doesn’t know what’s wrong? There are several treatment options that can help you get pregnant even with unexplained infertility.

Treatment Options

Unexplained infertility is generally treated empirically. This means a treatment plan is based on clinical experience and some guesswork. Sometimes a healthcare provider will advise trying to get pregnant without intervention, if you are willing, for at least six months to one year. If you are over the age of 35, though, they may explore other options after six months.

The most common treatment map for unexplained infertility includes making lifestyle changes like weight loss or smoking cessation and using Clomid or gonadotropins (to promote ovulation) along with intrauterine insemination (IUI) for three to six cycles.

If that is not successful, the next step is usually trying in vitro fertilization (IVF treatment for three to six cycles. Rarely, third-party IVF treatments (like using an egg donor or gestational carrier) are used.

Making Lifestyle Changes

Improving your overall health is important—especially when the cause of infertility is unknown. However, there’s no research showing that making these changes can actually help you conceive. But since these factors can be associated with decreased fertility, they are important to consider and address.

Given the shot-in-the-dark approach to unexplained infertility treatment, whatever lifestyle changes you and your partner make to improve your overall health can’t hurt and may actually help.

The most commonly suggested lifestyle changes to improve fertility naturally are for both partners to:

• Avoid excessive alcohol consumption
• Cut back on caffeine
• Lose weight (if overweight) and get regular exercise
• Reduce overall stress
• Quit smoking

Trying to Conceive Naturally

You likely do not want to hear from a healthcare provider that the first step is to “keep trying on your own” for another six months. However, in some cases, it may be a good plan—but only after testing has confirmed your diagnosis as unexplained.

"Expectant management" is when your healthcare provider doesn’t prescribe treatments right away, but does conduct basic fertility testing and may monitor the situation as you try on your own for a limited time.

A randomized clinical trial was conducted comparing expectant management with IUI plus fertility drugs for couples with a good prognosis. The study took place over a six-month period.

For the people who received IUI plus fertility drugs, 33% achieved pregnancy and 23% of the pregnancies were ongoing at study’s end. For the people who didn’t receive treatment and went the expectant management route instead, 32% got pregnant on their own and 27% of the pregnancies were ongoing at study’s end.

Building on this research, another study looked at what happens when couples are assigned a treatment plan based on prognosis. Prognosis was determined by their age and how long they had been trying to conceive on their own.

In this study, couples were assigned to one of three paths: start with expectant management, start with IUI with fertility drugs, or go straight to IVF treatment. A little more than 90% of the couples were assigned to the expectant-management group.

At the study's conclusion, 81.5% of couples achieved pregnancy. Of those pregnancies, 73.9% were conceived without fertility treatment. Those are excellent odds, especially when you consider success rates for infertility in general. When looking at all infertility causes and cases, live birth rates after treatment are just under 50%.

Using Clomid

Clomid is the most commonly prescribed fertility drug. It can help people who are not ovulating. It can also boost sperm production. The first doctor you see when trying to treat infertility is your gynecologist. They are most likely to prescribe you Clomid, even if you have unexplained infertility.

This may be a waste of time and expose you to risks and side effects for no benefit. In a study of 580 women with unexplained infertility, the women were randomized to one of three groups for six months of treatment. These groups included Clomid treatment, expectant management, and IUI alone (no fertility drugs).

Interestingly, when looking at the live birth rate for each group, Clomid had the lowest with 13%. The expectant management group experienced a 17% live birth rate and the IUI treatment group experienced a 22% live birth rate.

Another study found that there is no evidence that Clomid alone is an effective treatment for unexplained infertility. This meta-analysis of several randomized control trials of Clomid for unexplained infertility reviewed results of seven different studies of a total of 1,159 couples.

It is also important to remember that Clomid treatment is not harmless. Treatment is also only recommended for up to six cycles, due to the possible increased risk of cancer. If your provider suggests Clomid alone, discuss whether it would be better to continue trying on your own for a while longer, or whether they would consider moving straight to IUI with Clomid.

Making this change may require moving on to a fertility clinic and reproductive endocrinologist. Few gynecologists are comfortable with or experienced at administering IUI treatment.

Trying IUI With Fertility Drugs

For people trying to get pregnant with unexplained infertility, IUI alone or with fertility drugs has been shown to slightly increase the odds of pregnancy. Although the evidence isn’t very strong, IUI with fertility drugs may be worth considering as an alternative to the very high cost and invasiveness of IVF.

In one study, couples were randomized into three groups. One received three cycles of IUI and Clomid, one IUI with gonadotropins, and the third got IVF. Pregnancy rates were 7.6% per cycle for Clomid with IUI, 9.8% per cycle for gonadotropins with IUI, and 30.7% per cycle for IVF.

Gonadotropins are more expensive than Clomid and are more likely to lead to ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy. They may not improve pregnancy rates enough to justify those risks. Couples who tried IUI with gonadotropins before moving on to IVF took longer to get pregnant and spent more money on treatment overall.

How many cycles of IUI you should try depends on your age and your interest in pursuing IVF treatment if IUI should fail. For those who are open to IVF, three cycles of IUI with Clomid is likely a good enough trial before moving on to IVF.

For those who are not willing or able to pursue IVF treatment, research shows IUI with fertility drugs is worth trying for up to nine cycles.

Moving to IVF

When it comes to treating unexplained infertility, IVF has the best odds for pregnancy success. The pregnancy rates for IVF treatment are three times what they are for IUI with Clomid. These results will vary with age, however.

Only during IVF can egg quality, the fertilization process, and embryo development be observed closely. All that said, IVF is both invasive and expensive.

You might think going straight to IVF is the best choice, given its superior success rates. But it is actually better for the vast majority of couples to give IUI with Clomid a try first. Most insurance companies that offer any sort of IVF coverage require less expensive treatments to be attempted first.

That said, proceeding straight to IVF and skipping IUI may be the best choice if you are age 38 or older. This decision regarding IVF is something to discuss in detail with your healthcare provider.

Seeking Treatments Beyond IVF

When it comes to getting pregnant with unexplained infertility, there are other options if IVF alone is not enough or fails.

Reproductive Immunological Treatments

There is a theory that natural killer cells may play a role in unexplained infertility, repeated IVF failure, or recurrent miscarriage. Despite their name, “natural killer cells” are not a bad thing. You actually want them around. You just don’t want them to be overly reactive or to have too many of them.

Intravenous infusion with a substance known as intra-lipids during IVF treatment may reduce the impact of excessive natural killer cells. However, there currently is no strong evidence this treatment can improve IVF live birth rates.

Removal of Endometrial Deposits

Some believe that unexplained infertility may be caused by mild endometriosis. In this case, the endometrial deposits may not be causing pain or directly interfering with ovulation or the fallopian tubes, but their presence may increase “irritation” of the reproductive system.

Some healthcare providers suggest laparoscopic surgery to diagnose and remove mild endometriosis before IVF is attempted. Others only suggest it after repeated IVF failure. Whether this treatment can improve live birth rates is not clear.

Gamete Donation

If egg, sperm, or embryo quality problems are discovered during IVF, your healthcare provider may recommend using a gamete or embryo donor for your next IVF cycle. Egg donation is the most expensive option, followed by embryo donation, and then sperm donation.

Success rates for egg donors are generally high. Embryo donation success rates will vary depending on the source of the embryo.

Gestational Carrier

If IVF treatment repeatedly fails after embryo transfer, finding a gestational carrier or surrogate may be the next step. Using a gestational carrier is extremely expensive and not easily—or sometimes even legally—available in all areas. But for those who can afford and access gestational carrier services, it can be their path the parenthood. 

A Word From Verywell

If you are experiencing unexplained infertility and are struggling to get pregnant, it is important to know what your options are and discuss them with your healthcare provider. There are a number of factors to consider that will be unique to you and your situation; and you want to be sure you are choosing the correct path for you.