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Causes of female infertility

Learn about the different causes that affect female infertility. Contact us to speak to a fertility expert about your unique female fertility needs.

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If you’re struggling with conception or carrying a pregnancy to term, you may be experiencing female infertility. Fertility doctors can help you identify the source of your infertility, and recommend treatment based on your specific needs. Your doctors are here to help you understand and overcome issues that compromise your ability to conceive. 

First, let’s explore some common causes of female infertility. 

Egg-related infertility

To successfully conceive, the female reproductive system releases one young egg each month. If a woman is struggling with infertility, the challenge related to the female eggs can be divided into two categories: ovulation and egg quality and quantity. 

Ovulation-related infertility

If a woman does not have a regular menstrual period occurring every 24 - 35 days, this can be related to infrequent or absent ovulation. This results in infertility as there are no eggs present for fertilization. 

Women who report having a menstrual period every month and have symptoms such as breast tenderness prior to their monthly period are usually ovulating an egg. If a woman is not having a regular period and it’s deemed that she’s not ovulating, an evaluation is necessary to determine the cause. 

Reasons why ovulation does not occur regularly include: 

Polycystic ovary syndrome (PCOS) 

The diagnosis of polycystic ovary syndrome (PCOS) requires three of the following symptoms: menstrual irregularities, androgen excess, and the appearance of polycystic ovaries on an ultrasound. This condition affects 5 - 8% of reproductive aged women.

Primary ovarian insufficiency (POI) 

Primary ovarian insufficiency (POI) is when the number of eggs present in the ovaries is very low. As a result, the patient has irregular periods and symptoms of hot flashes. In order to meet criteria for this diagnosis, the patient must be under the age of 40 years.

Thyroid disease and high prolactin levels

If a woman has either low or high thyroid levels or has high prolactin (a milk-producing hormone released by the brain), this can lead to irregular ovulation.

Hypothalamic dysfunction

Hypothalamic dysfunction is a problem with the part of the brain called the hypothalamus, which controls the pituitary gland and regulates many bodily functions. This can occur if a patient is susceptible to certain stressors causing their brain to release subnormal amounts of the hormones necessary for ovulation.

Number and quality of eggs

The other cause of infertility related to the egg is the actual number and quality of the eggs present. Even if a woman is ovulating regularly each month, she may still have difficulties conceiving. In order to understand egg production, it is important to understand a little bit more about normal ovarian physiology. 

As a woman, you have the most eggs you’ll ever have when you’re in your mother’s uterus, which is approximately five to six million. By the time you’re born, there are around two million. At puberty, this number decreases to a couple hundred thousand, at age 37 - 38 around 25,000, and by menopause women essentially have no functioning eggs remaining. If your ovulation is regular, each month one of your eggs is ovulated and the rest present die off. Therefore, women have an exponential decline in the number of eggs. 

Additionally, because the eggs have been around since before we were born, they do not divide well leading to problems with the number of chromosomes in the egg itself. If the number of chromosomes in the egg is incorrect, this can lead to problems with the embryo implanting in the uterus and an increased risk of miscarriage. 

Doctors can determine if a patient is ovulating based on their menstrual cycle history and by testing their progesterone levels in the second half of their menstrual cycle. To evaluate the quantity of eggs in a woman's ovaries we test hormone levels called estradiol and follicle stimulating hormone (FSH) on the second or third day of the menstrual cycle. 

Age-related infertility

It’s impossible to review infertility and avoid consideration of the effect of age on fertility and egg quality. Many women are delaying childbearing into their late 30s and 40s, which has resulted in a significant increase in infertility due to the “Age Factor.” 

Many studies, including IVF success rates, demonstrate a significant drop in pregnancy rates as women get into their late thirties. Studies have shown that the chance of a 20-year-old woman conceiving after one month of exposure is at 30%. While, at 30 years this rate drops to 20% per month, and at 40 it’s 10% per month. At 45, there is less than a 2 - 3% chance of a woman conceiving on her own after trying for one cycle. Parallel to this, the miscarriage rate increases from 10% at the age of 20 to 40% at the age of 45.

The reason behind this phenomenon lies in the fact that egg quality deteriorates with time, which in turn translates to lower pregnancy rates. Unlike men’s sperm supply, women are born with a set number of eggs which they use up over the lifespan of their reproductive years. On the other hand, men generate new sperm in their testicles every 70 - 80 days, causing minimal effect to their fertility potential as they age. With time, the amount of eggs dormant in the ovaries will deteriorate, hence the lower fecundity rate. A direct correlation to this is the increased risk of chromosomal anomalies in infants born from older women. 

This is why it’s recommended that women over the age of 34 have an amniocentesis performed at 16 - 17 weeks of gestation to rule-out a chromosomally abnormal fetus. Studies also demonstrate that at or around the age of 37, there’s an accelerated loss in the quality and number of eggs, causing an acute drop in pregnancy rates in women older than 37. One of the most common causes of infertility in this age group is accelerated ovarian aging. A term used to imply that the ovaries at a certain age are behaving as if they are older. It is imperative that every woman seeking help for infertility be tested for her ovarian reserve.

Uterine-related infertility

Many conditions can affect the uterus itself and therefore make it more difficult for implantation of the embryo to occur. The uterus is connected to the vagina via the cervix and the inside of the pelvis via the fallopian tubes. The egg travels through these tubes after it is released from the ovary. 

Fibroids, an overgrowth of the muscle tissue in the uterus, can interfere with implantation and embryo growth depending on the location and size of the overgrowth. Uterine polyps, an overgrowth of the endometrial tissue of the uterus, can also impede implantation and embryo growth. Additionally, scarring inside of the uterus (Asherman's Syndrome) can cause uterine malformations like uterine septum's, and other problems with implantation and embryo growth. 

To determine if the inside of your uterine cavity is healthy, your doctors will perform a test called a hysterosalpingogram (HSG) or a saline sonography. During these tests, a dye is instilled into the uterus while imaging is performed to see if there are areas inside the uterus that do not fill up with the dye.

Tubal-related infertility

The fallopian tube functions to pick up the egg from the surface of the ovary upon ovulation. It’s here that the sperm and egg meet and fertilization occurs. Once fertilization occurs, the embryo travels through the fallopian tube for the next couple of days prior to being released into the uterus. 

The internal lining of the fallopian tube contains delicate hair-like projections that are instrumental in facilitating the transportation of the sperm, egg, and embryo through the inside of the tube. If a patient has a tube or tubes that are damaged or blocked, the sperm and the egg are not able to meet and fertilization cannot occur in the body. If fertilization does occur but the tube is damaged, it may not be able to transport the embryo to the uterus. 

Additional causes of tubal damage are: 

  • Sexually transmitted diseases such as Gonorrhea and or Chlamydia. If these infections remain undetected and are left untreated, they can permanently damage the tube’s delicate lining and cause scar tissue, which can lead to tubal blockage. 
  • Past history of surgery in the pelvis, such as removing ovarian cysts or surgery for appendicitis. 
  • Endometriosis, which can cause scarring, tubal damage and blockage. 

Your doctor can determine if the tubes are patent (open) by performing a test called a hysterosalpingogram (HSG). During this test, dye is instilled into the uterus and the tubes at the same time imaging is performed in order to see if the tubes fill up with the dye and ultimately spill the dye liquid into the pelvis.

Conditions that can result in tubal damage include: 

Pelvic infections

The most common cause of tubal disease is pelvic infection, secondary to sexually transmitted diseases Gonorrhea and or Chlamydia. These infections typically affect young sexually active women and sometimes go unnoticed by the individual. Often, the patient will have a vaginal discharge with pelvic pain for a few days before she seeks help. 

If caught in time, treatment with antibiotics will clear the disease without long term effects. In cases where treatment is not rendered, the bacteria can travel through the uterus and affect the tubes. The disease is called pelvic inflammatory disease (PID) and can be very serious if left untreated. 

Pelvic inflammatory disease (PID)

There are different levels of damage that can occur in these cases. In mild cases, only the lumen of the tube is affected but damage to the ciliated epithelium or lining can still result in infertility or ectopic pregnancy. In the more serious cases, the fimbriae are affected, causing the end of the tubes to be clubbed or blocked with fluid accumulation in the proximal part of the tube called hydrosalpinx. 

Infertility is the obvious outcome as the tubes will not be able to pick up the egg. The disease does not necessarily affect both sides equally in some patients and is still possible to have one side blocked while the other is still patent. However, in such cases, the patent tube is often non-functional because of damage to the luminal cells.

Endometriosis


Endometriosis remains one of the most common and puzzling gynecological disorders in women. Endometriosis is the presence of tissue similar to the lining of the uterus or endometrium that grows outside the uterus, on the tubes, ovaries, bowels and the peritoneum or lining of abdomen. Women with hereditary factors may have an increased tendency for endometriosis, and recent studies have suggested that the immune system may be involved. 

Doctors do not know the exact cause of this disease, but it is known that patients who have this diagnosis have a decreased fertility potential compared to those who do not. Doctors typically make the diagnosis of endometriosis based on a patient’s history and physical examination. However, the only way doctors can diagnose this condition for certain is to perform an operation and see if endometriosis is present. 

Endometriosis typically develops when women are in their 30s or 40s, but this condition may be seen at any time in reproductive-age women. It’s thought that 15% of infertile patients have endometriosis. Endometriosis goes through different stages. In stage 1, small implants are present inside the pelvis outside the confines of the uterus without any anatomical interference of egg pick-up. In stage 4, the ovaries and tubes may have extensive scarring and cysts and therefore direct interference would be present with the normal functionality of the tubes and ovaries. 

Endometriosis should always be considered a possibility in infertile patients, particularly in the presence of a family history or other symptoms suggestive of the disease. Premenstrual pelvic pain and worsening pain during periods and intercourse are the most common symptoms of endometriosis, although the degree of pelvic pain seems unrelated to the severity of the disease progression. 

Treating endometriosis can be difficult. If pain is your main complaint, surgical treatment with laparoscopy with “fulguration” or burning of the endometriosis is often very successful. And if you’re trying to get pregnant but can’t, it’s important to determine if the tubes are open. If they are, conventional treatment with ovulation induction and insemination can be tried for a few cycles and if unsuccessful proceed to IVF. In cases where there is anatomical disease with scarring and damaged tubes or ovaries, IVF would be the most suitable treatment from the outset.

Previous surgeries

Another common cause of tubal disease is the result of previous pelvic or abdominal surgical procedures. Possible procedures doctors can perform for gynecological conditions include ovarian cysts, endometriosis or fibroid tumors or non-gynecological conditions such as appendicitis or diverticulitis. Any time a “cut” is made in an organ such as the ovary or the uterus, the body will react by producing scar tissue in the ensuing weeks.

A deep cut usually results in scarring. Unfortunately, if the scarring affects crucial structures such as the Fallopian tubes, it could result in the  inability of the tube to move freely in order to pick the ovulated egg from the surface of the ovary. If the scarring affects the surface of the ovary, a “blanket” forms, covering and preventing the egg from pick-up. A history of pelvic or abdominal surgeries is a clear indication to test the integrity of the Fallopian tubes. In some cases, doctors may require a laparoscopy to rule out tubal scarring. In this procedure, a telescopic-like instrument is introduced through the umbilicus in an outpatient setting and the tubes evaluated.

Genetics

In rare instances, a woman is born with congenitally absent Fallopian tubes. Other anomalies usually accompany such conditions, such as an abnormal uterus or even ovaries. The diagnosis is usually reached following laparoscopic evaluation. Women born without fallopian tubes can still achieve pregnancy through In Vitro Fertilization.

Uterine disease

The uterus is the incubator for the zygote, which implants and grows within it. Any abnormality affecting this organ can result in infertility or even a miscarriage.

The body of the uterus is composed of “smooth” muscular tissue and the cavity is lined with a specialized layer of cells called the “endometrium.” This layer is crucial in the implantation process. The endometrium has to be devoid of any abnormalities and should reach a certain thickness to sustain a pregnancy. Hormones produced by the ovaries, Estrogen and Progesterone, help prepare the endometrium for implantation.

Fibroids

Fibroids, or myomas, are benign tumors of the muscle of the uterus. They are very common with almost 1 in 4 women harboring fibroids once during their lifetime. Fibroids are generally harmless and can attain different sizes under the influence of the estrogen hormone. If the fibroids are large, they can present symptoms such as discomfort, pain during intercourse, heaviness, urinary symptoms and abnormal bleeding. Fibroids shrink after menopause when the body’s estrogen levels drop. 

The location of fibroids is important in determining its harmfulness. They may be located in: 

  • The body of the uterus, called “Intramural” fibroids
  • On the outside of the uterus attached to it with a pedicle, called “Serosal or pedunculated” fibroids
  • Inside the uterine cavity or “Submucosal” fibroids.

When fibroids are large and close to the lining of the uterus, they must be removed before attempting to conceive again as it can interfere with implantation, cause infertility or increase the risk of miscarriages. 

Adhesions

Adhesions or scar tissue inside the uterine cavity can also interfere with fertility. The most common causes of adhesions include infection or previous surgical manipulation of the uterine cavity, such as Dilation & Curettage (D&C), fibroid or polyp surgery. 

Note: A D&C is the procedure in which the cavity of the uterus is scraped to remove abnormal tissue. Damage can occur when doctors  perform the procedure aggressively, following the delivery of a baby, or when it is complicated due to an infection. 

Many patients harboring such adhesions do not have any complaints or symptoms and it’s diagnosed during routine infertility investigations during a hysterosalpingogram or ultrasound examination. In some patients however, the scarring is so severe that there is absence of periods or very light periods as most of the endometrium is covered with scarring. Since the endometrium is what is “shed” during the menstrual cycle, having less of it results in lighter periods.

Congenital anomalies

Some women are born with congenital anomalies of the uterus, and this can encompass a variety of abnormalities that range from mild to severe. In some cases, the uterus is absent or extremely small. In other cases, the uterus is divided in two halves or a thick membrane, called a Septum, is present in the middle of the cavity.  

Such abnormalities can interfere with the normal implantation of the zygote and result in infertility or miscarriages. The diagnosis is usually made by the x-ray test called HSG or Hysterosalpingogram along with laparoscopy surgical exploration. Milder cases, such as a small septum, can be easily fixed on an outpatient basis. In extreme anomalies, surrogacy is the only solution for a successful outcome.

Unexplained infertility

If your doctor performs a complete investigation and no obvious cause of infertility is found, you’ll be given a diagnosis of exclusion. Most of the time, patients are labeled with this diagnosis without completing all the necessary testing. The prognosis of conceiving is not necessarily better if the diagnosis of unexplained infertility is made. To the contrary, it could indicate a cause that could be more difficult to treat. 

Occasionally, a diagnosis is reached following a treatment such as In Vitro Fertilization (IVF). For instance, a subset of patients suffer from infertility because of sperm with poor fertilization capabilities. When an IVF cycle is done in these patients, fertilization would be poor and therefore the diagnosis of male factor infertility is reached.

Side effects and complications of tubal disease

There are several possible side effects or complications from tubal disease. The dilated or swollen fallopian tube can cause pelvic pain. A patent but damaged tube is the most common cause for ectopic pregnancies. In these cases, the fertilized zygote gets “stuck” inside the tube and continues growing, causing pain and eventually rupturing. An ectopic pregnancy is a medical emergency in need of immediate attention.

Ovulation disease and disorders

The basis of reproduction is the presence of egg and sperm. Therefore, it is natural to look at the ovaries as the initial step in the investigation of the female partner.

Ovulation disorders and irregular menstruation

Your physician will first need to understand the pattern of your menstrual cycle. If this consultation confirms the presence of a regular cycle, the physician can be assured that the patient is producing an egg every month. An additional  way to confirm ovulation is by reviewing Progesterone hormone level with a blood test. 

The test needs to be done a week after expected ovulation. A level over 3 ng/dl confirms ovulation. An alternative way is by doing serial pelvic ultrasound examinations to visualize the maturing follicle (with the egg in it) and confirm its rupture a few days later. 

A woman will on average, ovulate 400 times during her lifetime. By the age of 50-51, she will deplete her stores of eggs and therefore menopause ensues. Unfortunately, several years before menopause or during the perimenopausal years, a woman will start having erratic ovulations and therefore irregular periods. This can be accompanied with symptoms of hot flushes, which is secondary to a decline in estrogen levels, because of the lack of regular egg production. 

Another instance of abnormal ovulation is the period immediately after puberty. For several months women may have irregular menstrual cycles because of erratic ovulation. Problems with ovulation are the most common causes of female infertility. These abnormalities can range from the occasional lack of ovulation and irregular periods to the total absence of ovulation with the resultant lack of any periods, which is known as amenorrhea.

Conditions associated with abnormal ovulation

Abnormalities related to weight

An individual’s body fat percentage plays an important role in the regulation of their menstrual cycle. If you experience a significant decline in body fat, you may experience the total absence of normal periods or irregular periods. This is why many underweight athletes, such as marathon runners or ballet dancers, suffer from infertility. Studies have also demonstrated that overweight women have a higher chance of having anovulatory infertility especially when their BMI is greater than 27 kg/m2.

Brain disease

Since the hormones governing the ovaries are released by areas of the brain called the hypothalamus and the pituitary gland, diseases affecting these areas such as tumors can cause abnormalities of ovulation. One such tumor is called a Prolactinoma that affects the pituitary gland.

Genetic causes

There are certain genetic conditions associated with abnormalities of chromosomes that can result in female infertility due to anovulation. One such common condition is a disease called Turner’s syndrome. These women lack one of their X chromosomes and are born with “streak ovaries”, which are not functional and cannot produce eggs. Some women suffer from a condition termed Premature Ovarian Failure. 

In these cases, due to an unknown genetic cause, the ovaries stop from functioning usually before the age of 40, which in turn results in amenorrhea or the absence of periods. The reason for the rapid depletion of eggs in these patients is not very clear.

Polycystic ovarian syndrome (PCOS)

PCOS is another common cause of female infertility. Many such patients also have other signs of the disease such as excess hair growth, especially on the face, inner thighs and lower abdomen. Some also suffer from excess body weight. There are other conditions associated with abnormal ovulation and the specialist will perform certain hormonal testing to determine the possible cause.

PCOS is one of the most common causes of abnormal ovulation and infertility in women. The exact cause of the disease isn’t well known but recent studies have demonstrated a clear link between PCOS and Insulin resistance, which may explain the link between PCOS and Diabetes. The higher insulin level leads to increased male hormones, which in turn lead to a disturbance of the ovulation cycle.

It’s also thought that some patients with PCOS have poor quality eggs due to the elevated male hormone levels and some suffer from an increased miscarriage rate. Some reports actually show a doubling of the rate. 

To treat PCOS, your doctor might involve ovulation induction with lower-risk oral medications, such as Clomiphene citrate or Letrozole, are used. In cases of failure, more aggressive treatment may be necessary with injectable forms of ovulation inducing medications. For some, In Vitro Fertilization (IVF) is needed as the ultimate therapy.

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