Female Infertility

What is Female Infertility?

Infertility is a medical issue that can have emotional, physical, mental, spiritual, and medical impacts on those who experience it. The unique thing about infertility is that it affects not just the individual, but also their partner. This piece will focus on female infertility, to discuss how it is evaluated, managed and treated. In order to understand infertility, it’s important to be familiar with the term ‘fecundability’, which refers to the likelihood of getting pregnant during one menstrual cycle. This basic knowledge allows doctors and healthcare teams to give the right advice and education on this health issue and make appropriate referrals.

Many studies have provided estimates of fecundability rates, which help provide a benchmark for normal pregnancy rates and thus aid in diagnosing infertility. For example, the largest of these studies found that 85% of women would become pregnant within a year. This same study found that the chances of conceiving, or fecundability, was around 25% in the first three months of unprotected sex, but that this decreased to 15% in the subsequent nine months. This research has been important in shaping recommendations for when couples should seek an infertility evaluation.

In line with this, the American Society of Reproductive Medicine (ASRM) recommends that couples consider an infertility evaluation if they have been unable to conceive after a year of unprotected sex, or after six months for women who are 35 or older. This includes those who have been trying to get pregnant through therapeutic donor insemination.

What Causes Female Infertility?

The World Health Organization (WHO) conducted a large study across different countries to understand more about infertility and whether it affects men and women equally. They found that in 37% of couples struggling with infertility, the issue was due to the female partner. In 35% of couples, both male and female partners had identifiable issues causing infertility; whereas in 8% of couples, it was due to problems related to the male partner.

In the same study, they identified the most common factors that led to issues with female fertility. These include issues with the ovulation cycle (25%), endometriosis, a condition where tissue from the uterus lining grows outside of the uterus (15%), pelvic adhesions, which are scar tissues in the pelvic region (12%), blockages in the fallopian tubes (11%), other abnormal conditions in the tubes or uterus (11%), and hyperprolactinemia, a condition with unusually high levels of hormone prolactin in the body (7%).

These causes will be explored further in later parts of this study. However, it’s important to know that problems unique to the male partner also contribute to a significant amount of infertility cases, even though they aren’t discussed in this particular study.

Risk Factors and Frequency for Female Infertility

A study by the National Survey of Family Growth, which interviewed 12,000 women in the US, discovered that a woman’s fertility tends to decrease as she ages. The results found that younger women have lower rates of infertility, while older women experience higher rates. Infertility rates were between 7.3 to 9.1% for women aged 15 to 34, while women aged 35 to 39 saw an increase in infertility rates to 25%. Moreover, women aged 40 to 44 had a 30% chance of infertility.

Infertility is a global issue, with higher rates in regions like Eastern Europe, North Africa, and the Middle East. Across the world, 2% of women aged 20 to 44 had never been able to give birth, and 11% of women who had previously given birth could not have another child.

• As a woman ages, her fertility typically decreases.
• Women aged 15 to 34 have infertility rates ranging from 7.3% to 9.1%.
• Infertility rates rise to 25% for women aged 35 to 39.
• Women aged 40 to 44 have a 30% chance of infertility.
• Infertility rates are high in Eastern Europe, North Africa, and the Middle East.
• Worldwide, 2% of 20 to 44-year-old women have never been able to give birth.
• Furthermore, 11% of women who have previously given birth cannot have another child.

Signs and Symptoms of Female Infertility

If a woman has been trying to get pregnant for 12 months (or 6 months if over 35) without success, it may be time to seek a fertility evaluation. This involves a thorough check of both the woman and her partner. Women preparing to use a donor sperm are advised to take the same fertility tests before insemination begins. Here are important factors that doctors usually look into:

• How long the couple has been trying to conceive
• The woman’s pregnancy history
• The woman’s period history, including any related symptoms
• Details about the woman’s medical, surgical, and gynecological history, especially past incidents of sexually transmitted infections
• Information about the woman’s sexual activity, like how frequent and at what times
• The man’s ability to maintain an erection and ejaculate
• Details about the couple’s lifestyle, including smoking, alcohol and drug use, exercise habits, diet and nature of their jobs
• If there’s a family history of genetic issues, vein clotting diseases, repeated pregnancy losses, or infertility

Doctors will also perform a thorough physical examination that includes:

• Measuring vital signs and BMI (Body Mass Index)
• Checking the thyroid
• Performing a breast exam to check for any abnormal milk production (galactorrhea)
• Looking for signs of excess male hormones (androgens): this may involve a skin and external genitalia exam
• Examining the vagina and cervix to spot any abnormalities
• Feeling for any pelvic masses or tenderness
• Checking for a larger or irregular-shaped uterus
• Using a transvaginal ultrasound, which is usually carried out on the spot as part of the initial physical exam

Testing for Female Infertility

In simple terms, there are 5 main methods of diagnosing problems related to fertility. These are semen analysis, checking how well the ovaries and uterus are working, examining the fallopian tubes, and conducting some hormone blood tests.

A necessary part of this process is assessing the semen in male patients. However, we’ll focus more on the evaluation of female patients in this discussion.

Firstly, doctors check how well the women’s ovaries are functioning. This can be quite straightforward – if a woman has a regular menstrual cycle with typical symptoms of bloating, fatigue, and breast tenderness, she is likely ovulating. Ovulation can also be detected with at-home urine tests that reveal a mid-cycle surge in a hormone called LH, or with a blood test for the hormone progesterone about a week before menses (period). An even more accurate but invasive method involves daily ultrasound examinations.

Doctors also assess the ovarian reserve, which is basically the number of eggs a woman has left. This can be done by measuring two hormones: FSH and estradiol on the 3rd day of the menstrual cycle, and Anti-Mullerian hormone (AMH) which can be measured at any time. A good ovarian reserve is indicated by small amounts of FSH and Estradiol. On the contrary, large amounts of these hormones imply a poor ovarian reserve, reducing the likelihood of natural ovulation and subsequent pregnancy. AMH is a hormone expressed by small egg-containing cells in the ovaries. Low levels of this hormone indicate that a woman may struggle to make more than a few mature follicles (eggs), while high levels are associated with a risk of ovarian hyperstimulation syndrome, which can happen during fertility treatments.

Remember, these tests can predict if a woman will have difficulties with ovulation induction, but they cannot predict whether a live birth will result. Also, they should not be used to exclude patients from fertility treatments like IVF.

Furthermore, there are also tests to assess how many small follicles are in the ovaries, which could indicate the ovarian reserve.

The patency (openness) of the fallopian tubes can be examined using a procedure called laparoscopy, which checks for blockages and abnormalities. But usually, a more common and less invasive procedure called a hysterosalpingogram (HSG) is preferred. It’s especially good at finding blockages at the start and end of the fallopian tubes, though it’s not so good at detecting internal or uterine adhesions. Interestingly, HSG can also increase rates of pregnancy and live births when an oil-soluble substance is used.

Finally, the inner part of the uterus can be examined. Though hysteroscopy, where the doctor visually inspects the uterus, is the best method for this, it’s more usual to conduct a less invasive ultrasound procedure called a saline infusion sonogram (SIS). This test is pretty good at finding any problems in the uterus that could affect fertility, making it an excellent screening tool before starting any infertility treatments.

Treatment Options for Female Infertility

If you’re a woman having difficulty conceiving, your body weight might be a factor. Women who are extremely underweight (with a body mass index, or BMI, less than 17 kg/m^2) often have issues with ovulation, especially if they engage in intense exercise or have eating disorders. They may develop a condition known as hypogonadotropic hypogonadism, which leads to decreased reproductive hormone production. Nonetheless, various interventions are available to stimulate ovulation, including the use of fertility drugs.

On the other hand, if a woman’s BMI is above 27 kg/m^2 and she experiences abnormal ovulation, weight loss alone can improve this condition. Losing 10% of body weight can restore normal ovulation in a large number of women in less than a year. Importantly, even if weight loss is beneficial for overall health, it is not the sole determinant of fertility. Therefore, women can still undergo fertility treatment without reaching a specific BMI.

Two commonly used medications to treat infertility are clomiphene citrate and letrozole. Clomiphene is a selective estrogen receptor modulator that works to increase reproductive hormone release, thus supporting ovulation. Letrozole, on the other hand, prevents estrogen production, also supporting ovulation in the process. Both of these medications can be used in conjunction with sexual intercourse timed around the body’s ovulation cycle to increase chances of pregnancy.

More involved treatments can involve the use of gonadotropins, which support the ovaries in producing more eggs. While this method requires close monitoring through ultrasounds, it can be very useful for women who have not found success with other treatments.

If a woman’s infertility is related to issues with the fallopian tubes or presence of pelvic adhesions, in vitro fertilization (IVF) is often recommended. Likewise, issues such as fibroids, polyps or other structural abnormalities within the uterus may also impact fertility rates. Surgical removal or correction of these may help increase chances of conception.

The IVF procedure involves stimulating egg production in the ovaries, retrieving the eggs, and then fertilizing them outside of the body. The fertilized eggs or embryos are then returned to the woman’s uterus, where they can potentially implant and lead to a successful pregnancy. Additional procedures, like genetic testing of the embryos, can also be performed to enhance the chances of a healthy pregnancy.

What else can Female Infertility be?

Infertility is a complex problem that can affect a couple deeply. It’s crucial to understand that there can often be many reasons behind infertility. Diagnosing infertility can be a lengthy and thorough process to ensure no underlying health issue is overlooked. This article will focus on diagnosing Polycystic Ovary Syndrome (PCOS), a common condition in people struggling with infertility.

When PCOS is suspected, doctors will consider other conditions that may cause similar symptoms, including:

• Ovarian tumors that produce androgens
• Adrenal gland tumors
• Nonclassic congenital adrenal hyperplasia
• Cushing syndrome
• Prolactinemia disorders
• Thyroid disorders

As part of the investigation for PCOS, doctors will run certain hormone tests, including total testosterone, DHEA-S, and 17-hydroxyprogesterone. These are mainly to rule out ovarian or adrenal gland tumors or nonclassical congenital adrenal hyperplasia (CAH). Also, tests for prolactin and thyroid-stimulating hormone might be necessary.

• The normal maximum level of testosterone for women is about 45 to 60 ng/dL.
• If a woman’s testosterone level is more than 150 ng/dL, doctors will need to check for tumors in the ovaries or adrenal glands that might be secreting androgens.
• A DHEA-S level over 500 to 700 mcg/dL implies the need to investigate for an adrenal tumor.
• If the level of 17-hydroxyprogesterone measured while fasting during the follicular phase (the phase of the menstrual cycle during which follicles in the ovary mature) is more than 200 ng/dL, an ACTH stimulation test is needed. A level above 500 ng/dL usually indicates non-classical congenital adrenal hyperplasia (CAH).

Understanding these medical conditions and performing further tests to investigate them are beyond the scope of this article.

What to expect with Female Infertility

This part will discuss the likelihood of pregnancy for each treatment option. The information largely comes from research into unexplained infertility but it also applies to known causes. The percentage for in vitro fertilization (IVF – a method of helping you get pregnant where eggs are removed from the woman’s ovaries and fertilized with sperm in a lab) changes a lot according to various personal factors. The following percentages come from an analysis of 45 different studies:

• No treatment: 1.3% to 3.8%
• Artificial insemination (IUI – when sperm is directly inserted into a woman’s womb): 4%
• Drug called clomiphene citrate (CC) alone: 5.6%
• CC with IUI: 8.3%
• Group of hormones called Gonadotropins alone: 7.7%
• Gonadotropins with IUI: 17.1%
• IVF: 20.7%

Using the drug letrozole alone, or letrozole with IUI, results in similar pregnancy rates as using CC with IUI. These treatment options can be used for women for whom IVF is not suitable and who have not been successful with CC and IUI.

In 2009, a study suggested that women who were not successful with CC and IUI should proceed directly to IVF, rather than trying gonadotropins and IUI before IVF. This approach led to getting pregnant faster, fewer treatment cycles, and lower overall costs per birth. While IVF pregnancy rates have increased since that study, the findings still show that IVF offers the best chance of getting pregnant compared to other treatments.

Previous research indicated that the use of clomiphene alone could be the first choice of treatment for infertility. However, this is no longer the case. In 2008, a randomized control trial found that using clomiphene alone resulted in fewer live births compared to just waiting and seeing what happens (14% versus 17%). The study did find a benefit in terms of patient satisfaction compared with waiting and seeing, but most women in both groups were satisfied with their care. Because of this study, the American Society for Reproductive Medicine (ASRM) recommended against using clomiphene with timed intercourse as the initial treatment for unexplained infertility.

Possible Complications When Diagnosed with Female Infertility

The three main complications related to infertility treatments are having multiple babies, ectopic pregnancy, and a condition known as ovarian hyperstimulation syndrome.

Multiple Births

Infertility treatments can significantly increase the chance of having more than one baby at a time. In the US, about 32% of pregnancies resulted from artificial reproduction methods were multiple births, compared to only 3.4% of those conceived naturally. The risk varies based on the type of treatment used. Medications like clomiphene and letrozole carry a lower risk than gonadotropins, which are hormones used to stimulate the ovaries. To manage this, health organizations advise using a process called elective single-embryo transfer (eSET) for patients with a good prognosis. This method has reduced the rates of twins and triplets to less than 1%.

Ectopic Pregnancy

An ectopic pregnancy is when the egg implants outside the uterus, usually in the fallopian tubes. This is a serious risk following infertility treatments and requires careful advice. The risk is two to three times higher in people undergoing treatment for infertility. The highest risk is amongst patients who have had surgery to correct issues with their fallopian tubes. Various studies have shown a range of ectopic pregnancy rates following different fertility treatments, with some as high as 30%.

Ovarian Hyperstimulation Syndrome

This is a rare but potentially dangerous condition that can develop as a result of fertility drugs used to stimulate the production of eggs. Symptoms can range from mild, such as bloating and nausea, to severe, including kidney failure and blood clots. This complication is more common in women with more than 20 mature follicles who have also received a hormone injection to trigger ovulation. Despite the potential severity, the rate of moderate and severe Ovarian Hyperstimulation Syndrome with IVF is between 1% and 6%.

Top Infertility Treatment Complications:

• Multiple births
• Ectopic pregnancy
• Ovarian Hyperstimulation Syndrome

Preventing Female Infertility

If a woman has been trying to become pregnant for a year through regular unprotected sex, or for six months if she’s over 35, it’s recommended that she see her healthcare provider for a referral to a specialist in fertility issues. It’s crucial to realize that difficulties in getting pregnant can come from either the woman, the man, or both.

Typically, the woman’s healthcare provider is the first one consulted in cases of infertility, but it’s essential not to overlook the potential contribution of the male partner to the problem. The treatments that are available for women having difficulty getting pregnant are well-researched and their risks are well-documented.

A woman considering these treatments should be informed of the possibilities of multiple pregnancies, an ectopic pregnancy (where the pregnancy occurs outside the womb), and Ovarian Hyperstimulation Syndrome (a reaction to fertility drugs). Additionally, she needs to know what her chances are of becoming pregnant with each treatment cycle. It’s also important to consider that there are no guarantees – even with treatments such as In Vitro Fertilization (a procedure where the egg and sperm are fertilized outside the body), there’s a chance that becoming pregnant might remain challenging.

Before she commits the significant time, money, and emotional resources that these treatments require, she needs to understand all of these potential outcomes fully.