Primary Ovarian Insufficiency (Premature Ovarian Failure)

Treatment, Causes, Diagnosis, and Family Building Options

Young couple hugging in sunlight, offering each other support after premature ovarian failure diagnosis
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Primary ovarian insufficiency (POI) is a potential cause of female infertility. Also known as premature ovarian failure, women with POI don’t ovulate regularly and are unlikely to conceive with their own eggs. The most successful fertility treatment option is IVF with an egg or embryo donor. 

Women with POI experience clinical signs and sometimes symptoms of menopause before age 40. (The average age of menopause is between 48 and 55.) This disorder may also be referred to as hypogonadotropic hypogonadism (HH) or primary hypogonadism.

POI is not menopause. While the disorder was once also called “premature menopause,” this name is inaccurate. Women who have gone through menopause don’t get periods, can’t ovulate, and can’t get pregnant with their own eggs. 

Women with POI may occasionally ovulate and may have a return of regular menstrual periods (even years after diagnosis). Also, conception with their own eggs isn’t completely impossible. (More on this below.)

Primary ovarian insufficiency isn’t a common cause of infertility, but it isn’t rare either. The risk of diagnosis increases with age:

  • 1 in 1,000 women ages 15 to 29 are diagnosed with POI
  • 1 in 250 for women ages 30 to 35
  • 1 in 100 for women ages 35 to 40

Receiving a diagnosis of primary ovarian insufficiency can be devastating. When your doctor tells you that your odds of having a child genetically related to you are extremely unlikely, you may feel confused, angry, and deeply sad. You may feel shame and even hopelessness. At first, you may feel apathetic or confused. These are normal feelings to have. If you have received this diagnosis, please reach out for support. ​Talk to your doctor, a therapist familiar with infertility, and, if possible, an infertility support group, so you can grieve and more fully explore your options. With time for healing, it is possible to have a full and happy life with primary ovarian insufficiency. 

Why Is It Difficult to Conceive With Primary Ovarian Insufficiency?

The ovaries of a healthy adult woman contain tens of thousands of follicles. In each follicle is a potential egg. Only a small percentage of these follicles will ever mature, ovulate, and have the potential to become an embryo. It’s natural and normal for the follicles to decrease with time. Case in point, a healthy baby girl is born with over 1 million eggs. But by the time she reaches puberty, she’ll already be down to just 300,000. 

It’s also normal for the follicles to eventually stop responding effectively to the hormones that trigger egg growth and ovulation. This is the cause of age-related infertility, and why women age 40 and up are less likely to conceive than a 30-year-old woman. 

However, in women with primary ovarian insufficiency, their ovaries don’t function as expected. The ovaries may have fewer follicles than what would be expected for a woman their age. Their antral follicle count (a method of estimating the general total of available follicles in the ovaries) will be low. 

Also, their ovaries and follicles won’t respond effectively to the hormones meant to stimulate egg maturation and ovulation. The ovaries may also fail to produce normal levels of estrogen. This is why fertility drugs aren’t necessarily effective in women with POI. 

Fertility drugs will only work if there are enough follicles in the ovaries to be stimulated and if those follicles will respond when exposed to ovulation-stimulating hormones. In POI, the follicles “ignore” or at least don’t fully respond to fertility drugs. Clomid or gonadotropins typically fail to stimulate healthy egg development or ovulation. Even if they can trigger ovulation, the eggs may be poor quality. This makes fertilization and pregnancy less likely. 

Symptoms of Primary Ovarian Insufficiency 

Primary ovarian insufficiency is a spectrum disorder. Some cases of POI are worse than others. This also means women will have varying degrees of symptoms. The most common symptom is irregular periods. Women with POI may

It is also possible for a woman with POI to go without regular menstrual cycles for years, and then suddenly start menstruating again. 

Some, but not all, women with POI experience symptoms from low estrogen levels. These symptoms may be constant or come and go. These symptoms may include:

If you have irregular cycles but don’t have these low estrogen symptoms, does that mean you don’t have POI? Not necessarily. Between 50 and 75 percent of women with POI will ovulate and release estrogen occasionally. (This is unlike a woman who has gone through actual menopause. After menopause, ovulation and pre-menopause estrogen levels don’t occur at all.) 

However, before you worry, there are many possible causes for irregular or absent ovulation. Less than 10 percent of women with anovulation will be diagnosed with POI. More common causes of irregular ovulation include polycystic ovarian syndrome (PCOS), hyperprolactinemia, and obesity-related infertility

Fertility Testing and Making a Diagnosis of Primary Ovarian Insufficiency

A diagnosis of primary ovarian insufficiency cannot be made on symptoms alone. There are other possible causes of irregular cycles and low estrogen levels, besides primary ovarian insufficiency. Your doctor may order the following tests before diagnosis:

  • A pregnancy test (to confirm this isn’t why your periods have stopped)
  • FSH levels (will be at menopause levels with POI)
  • Estradiol (estrogen) levels (often low in women with POI, but not always)
  • AMH (to evaluation overall ovarian reserves)
  • Prolactin (to rule out hyperprolactinemia)
  • Antral follicle count (an ultrasound, also to evaluate ovarian reserves) 
  • Clomid challenge test (to evaluate how your ovaries respond to fertility drugs) 

If your FSH levels are unusually high and in the menopausal range, your doctor will likely reorder the test for a month later to confirm.

If the results repeat, and you are age 40 or younger, your doctor may diagnose you with POI. 

What Causes Primary Ovarian Insufficiency?

For the majority of women with POI, it will remain unknown what caused the syndrome.

Primary ovarian insufficiency is associated with a number of autoimmune diseases, including dry eye syndrome, rheumatoid arthritis, and lupus. However, how they are related is not clear. Some cases of POI are due to genetic mutations. Fragile-X and Turner syndrome can cause POI. 

However, new genetic research has found that as many as 20 to 25 percent of POI cases may be caused by genetic factors (including Fragile-X and Turner syndrome.) This is still in the early stages of research, so more accurate testing isn’t yet available. In the future, however, genetic testing may be able to further identify those at risk. 

Given the possible genetic connection, it’s not surprising that a family history of primary ovarian insufficiency occurs in 10 to 15 percent of cases. It’s unknown whether women with primary ovarian insufficiency are born with fewer eggs or if their fertility declines more rapidly. 

Primary ovarian insufficiency can also be caused by medical treatments. Some cancer treatments, including chemotherapy, radiation, and surgery, may lead to POI. Primary ovarian insufficiency that occurs shortly after treatment is known as acute ovarian failure. It’s important to know that decreased fertility after cancer treatment is not always permanent. Whether your fertility will return partially or fully will depend on your age when you received the cancer treatment and what cancer treatments were used. 

If you’ve been diagnosed with cancer, and you have not yet started cancer treatment, talk to your doctor about preserving your fertility. It may be possible to freeze your eggs or ovarian tissue

Fertility Treatment for Primary Ovarian Insufficiency

The best and frequently only fertility treatment option for women with spontaneous primary ovarian insufficiency is IVF with an egg or embryo donor. 

If in addition to POI there are uterine problems, a surrogate may also be needed to carry the pregnancy. But this isn’t common.

The egg or embryo donor may be a known donor—a friend or family member—but more often, the donor is unknown. Your fertility clinic may help you find an egg donor, or you may work with an egg bank or agency. 

An embryo donor may be arranged through your fertility clinic or an agency. Be very wary of online advertisements and offers for egg or embryo donation. There are people out there looking to scam desperate parents out of their money.

IVF with an egg donor is highly successful. In fact, egg donor IVF has the highest success rates of all IVF treatment options. One study found that women who finished three IVF cycles with donor eggs had a 90 percent chance of pregnancy success. Cost is the biggest obstacle to egg donor IVF. One fresh egg donor cycle may be between $25,000 to 35,000. When you consider that you may need to do multiple cycles, the costs can quickly become overwhelming.

Using frozen eggs from an egg bank can be slightly less costly, as can “sharing” an egg donor with another couple. Another way to reduce costs is to have a known-donor, like a friend or family member. However, the cycle may still be in the $15,000 to 20,000 range. 

Embryo donor IVF is significantly less costly, and even cheaper than regular IVF. According to RESOLVE, the average embryo donor cycle at a fertility clinic costs between $2,500 and 4,000. However, that fee doesn’t include legal and the required psychological counseling. The fee may be higher if arranged through an agency. 

Success rates for embryo donation vary considerably. It will depend on the fertility clinic, the couple’s fertility situation who donated the embryos, and whatever uterine factors may be at play for you. 

Making the decision to use an egg or embryo donor can be emotional and difficult. Acknowledging you may not be able to have a genetic offspring can be heartbreaking.

Choosing an embryo donor means that both you and your partner will not be genetically related to the child. With egg donation, only you will not be genetically related. 

Counseling with a therapist experienced with fertility issues is not only highly recommended but also required by most clinics before treatment begins. 

Can I Get Pregnant With My Own Eggs? Will I Need to Use an Egg Donor?

Women who have gone through cancer treatment may be able to use their own eggs or embryos if they took steps to preserve their fertility before treatment. That may have included egg freezing (vitrification), ovarian tissue freezing, or embryo cryopreservation.

Also, some women who experience POI after cancer treatment may have ovarian function return. If you are trying to conceive after cancer, talk to your doctor about your options. If you have not gone through fertility preservation prior to diagnosis, conceiving with your own eggs is unlikely. However, it is not impossible. Research has found that 5 to 10 percent of women diagnosed with primary ovarian insufficiency have gone on to conceive, sometimes spontaneously. This may occur with or without fertility drugs. It also seems to be more common in women receiving hormone therapy (meant to address the low-estrogen symptoms of POI.) 

Some women go into a temporary remission and may have their ovaries begin to function again. They may have their menstrual cycles return after years of irregular or absent periods. It’s not well understood why some women go into remission or conceive and others do not. Your doctor cannot predict if this will be your situation. If you really want to have a child, hoping you’ll fall into the lucky 5 to 10 percent group is not a good plan.

There is evidence that some women with POI may be able to ovulate and conceive with their own eggs if they receive estrogen therapy prior to fertility drug use. Research on this method—estrogen therapy followed by treatment with gonadotropins—has received mixed results. While a few studies found a degree of success, others have not. Keep in mind that the success rates for fertility drugs, IUI, or IVF with your own eggs is very low. 

Given the cost of treatment, plus the emotional strain of unsuccessful fertility treatment cycles, moving straight to IVF with donor eggs or embryos may be the smartest move. Of course, get a second opinion. Don’t go straight to IVF with an egg donor without consulting with more than one doctor. However, you also don’t want to waste financial and emotional resources on treatments that are unlikely to succeed. 

Note: if you do not want to get pregnant, and you have POI, you should not rely on regular birth control pills (or your infertility diagnosis) for contraception. Birth control pills have not been studied in women with this disorder. Women with POI have conceived on birth control pills and on hormone therapy. If you want to avoid pregnancy, a barrier method or intrauterine device may be better. 

Alternative Options Besides Fertility Treatment

While IVF with an egg or embryo donor is likely your primary fertility treatment option, it is not your only family building option.

Some couples decide to pursue adoption or foster parenting. They may consider adoption from the start, or move onto adoption if treatment fails. 

Choosing a childfree life is an additional option. A counselor can help you consider all of your choices, so you can make an informed decision. 

Additional (Non-Fertility) Testing After a Diagnosis of POI

POI is associated with other health problems. For this reason, your doctor may order further testing, including:

  • A bone density test: Low estrogen levels put you at risk for osteoporosis. Hormone therapy, a healthy diet, and weight-bearing exercise can lower your risk.
  • Karyotype and genetic testing: Some cases of POI are caused by gene mutations. Some women may only have one X-chromosome instead of two. 
  • Genetic testing can also check for the FMR1 gene, which is associated with Fragile X syndrome and POI. 
  • Thyroid hormones: Women with POI are at risk for thyroid imbalances. In fact, between 14 and 27 percent of women with POI will also have low thyroid. 
  • Cortisol level or a corticotropin (ACTH) stimulation test: Women with POI are at risk for adrenal gland problems.
  • Research has found that approximately 3 percent of women with primary ovarian insufficiency may develop Addison’s disease.  
  • Autoimmune testing: Up to 20 percent of women with POI will experience other immune disorders. 

Women with primary ovarian insufficiency are more likely than the general public to have these additional health problems, but it is not a given you will face them. 

As always, talk to your doctor if you have questions or concerns. 

Physical and Emotional Health After a Diagnosis of POI

Women with low estrogen levels are at a higher risk for heart disease, difficulties with sex (including painful intercourse), and osteoporosis. 

One possible treatment your doctor may recommend is hormone replacement therapy. Usually a combination of estrogen and progesterone, this may relieve some of your symptoms and might reduce your risk of osteoporosis. Hormone therapy can also help with hot flashes and low mood associated with low estrogen. Treatment is usually only continued until the average age of menopause when it would be normal to have low estrogen. As with all treatments, there are possible risks and benefits. No one really knows what the long-term risks are of hormone treatment (or not doing hormone treatment) in women with POI. Discuss your treatment options with your doctor.

Women with primary ovarian insufficiency may also experience depression and/or anxiety. This is partially because of the low estrogen levels, but also, the diagnosis and resulting infertility can also lead to emotional distress. If there are adrenal or thyroid problems, these can also cause low mood. 

Counseling is highly recommended. A professional therapist, especially one familiar with infertility, can help you cope with the diagnosis and make informed decisions on your family building options.

An anti-depressant may also be helpful. Don’t assume you can’t take one if you’re trying to conceive. This is something to discuss with your fertility doctor, primary care physician, and counselor. 

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Article Sources
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