Infertility. Why me ?

The famous Aphrodite and Venus were considered to be the Goddesses of fertility in the Greek and Roman mythologies respectively. Actually, tens of other fertility Gods and Goddesses have been described across different civilizations and historically couples used to pray for their respective deities in hope of conceiving. Today, after thousands of years some people still hold superstitions concerning a woman’s fertility, and women tend to be blamed for not being able to conceive! This belief of a woman’s hostile environment standing in the way of natural conception is still being portrayed in some parts of our current “modern” world.
Infertility is commonly seen nowadays, and it has been shown to be linked to psychological, economic and medical burdens. Couples tend to seek fertility counseling much more often than before, and this is mostly secondary to their understanding that infertility is not something to be ashamed of, it has solutions and it should be handled by specialists.

The aim of this article is to address the definition of infertility, its causes and risk factors, in addition to its appropriate evaluation and potential treatment.

What is infertility?

Studies have shown that around 80% of “apparently normal couples” will be able to conceive during the first 12 months of regular unprotected sexual intercourse. After this 12 months period the chance of natural conception becomes much lower than expected (5-15%).
Also, a woman’s ability to naturally conceive decreases with her advancing age, this decline in “fecundability” is likely caused by a decrease in the quality as well as the quantity of a woman’s eggs. So, based on that, infertility is defined as a couple’s inability to conceive after 12 months of regular sexual intercourse without the use of any contraceptive method in women aged less than 35 years, and after only 6 months in women aged 35 or more.
Another subset in the definition of infertility is “primary” versus “secondary" infertility. With “primary” infertility the couple has never had any prior pregnancies, whereas in secondary infertility, the couple used to be able to naturally conceive and then was not able to do so anymore.

The prevalence of infertility was noted to be different across different studies, as some reported a 6% while others a 15% prevalence. Also, the frequency of infertility changes across different age groups as 9% of young women (15-34 years) and up to 30% of women aged 40-44 years had primary infertility. This discrepancy among studies have been postulated to be secondary to many reporting biases and confounding variables, so the generally accepted prevalence of infertility is 15%.

What causes infertility?

Unfortunately, many cultures and societies find it easy to blame the woman for a couple’s infertility, and this stems from the belief that a “healthy woman” will be able to conceive and a “sick woman” is more likely to be infertile. However, this assumption is not valid, as people should understand that for a pregnancy to occur, we need a sperm and an egg.
Any defect in the sperm can cause infertility too. So according to the World Health Organization (WHO) infertility can be secondary to male factors alone (30%), female factors alone (30%), male and female factors together (20%) and unexplained factors (20%). Which means that the male factor plays a role in around 50% of cases of infertility!
A fertile man should have a healthy “seed” that is able to fertilize the woman’s egg. This “seed” we medically call “sperm”, can be absent, low in number or defective in shape, size, motility… so, it is quite simple; a male infertility is secondary to a defect in his sperm! This defect can be secondary to many genetic, hormonal and environmental factors such as congenital malformations and syndromes, irradiation, surgeries, chemotherapy, medications, varicoceles, infections and exposure to hyperthermia (elevated temperatures). 
As for the women, they should have a healthy reproductive system in order to be able to conceive too. A woman should be able to ovulate regularly (release an egg on a “monthly” basis), she should have healthy fallopian tubes (where fertilization of the egg by a sperm occurs) and she should have a normal and well receptive uterus (where the fertilized egg implants and grows). Any condition that can negatively impact the ovarian reserve, tubal function or uterine cavity can be associated with female factor infertility.

So, let’s dwell further into the factors that can affect a woman’s fertility!

Ovarian Reserve

If the woman is not ovulating, she will not be able to get pregnant. Also, if she is ovulating in an irregular manner, she would find it difficult to conceive. The basic thing through which you can tell if you are ovulating regularly or not, is your period! If you have regular “monthly” periods you are most likely ovulating, whereas if menses are irregular or absent you are most probably ovulating irregularly or not ovulating at all, and you will have difficulty getting pregnant.
Furthermore, as I have previously mentioned, with advancing age the woman’s ovarian reserve is expected to decline, and thus a woman’s ability to spontaneously conceive wanes too. With age, not only the number of oocytes (eggs) is affected, but their quality diminishes as well, which in turn is linked to infertility, chromosomal syndromes, malformations and miscarriages in older women.
Besides age, factors that affect a woman’s egg reserve include (not limited to), infections, genetics, autoimmune diseases, chemotherapy, ovarian surgeries and radiation.

Healthy Fallopian Tubes

As stated before, healthy tubes are needed for adequate transport of the egg and the sperm, and it is the place where normal fertilization occurs. Defects in the tubes, causing infertility, can be secondary to pelvic inflammatory diseases (due to sexually transmitted infections such as chlamydia and gonorrhea), pelvic surgeries, bowel inflammatory conditions (appendicitis and inflammatory bowel diseases), and endometriosis (see section below).

Healthy Uterus

Of course, the pregnancy occurs in the uterus, and thus a healthy uterus is a must in order for a pregnancy to take place. Many uterine structural pathologies were linked to primary and secondary infertility such as, uterine fibroids (check my article “Uterine Fibroids; The truth behind them!” on https://onlinewomenhealth1.blogspot.com/2020/07/uterine-fibroids-truth-behind-them.html), polyps, adhesions and uterine anomalies (such as uterine septum). Not only the structure should be normal, but also the endometrial receptivity should be adequate for implantation to take place and this receptivity is hormonally mediated.

Endometriosis

We all hear a lot about endometriosis which signifies “wondering” endometrial glands and tissues that are outside the uterine cavity. They can virtually be found anywhere in the abdomen and pelvis. The major symptoms of endometriosis are, painful periods, painful sexual intercourse, painful defecation and urination, in addition to infertility. Endometriosis can cause infertility through different mechanisms:

• Anatomic distortion from pelvic adhesions (can cause tubal defects)
• Decrease in the ovarian reserve secondary to endometriomas (chocolate/old blood cysts on the ovaries) and ovarian surgeries
• Production of inflammatory molecules that negatively affects the egg quality and renders the pelvic area hostile to natural conception.

Healthy Cervix 

Even though we do not talk about it much in fertility counseling but the cervix (the structure between your vagina and uterus) mediates the entry of the sperm to the uterine cavity. So congenital or acquired (post-surgical) malformations in the cervix can cause narrowing in the canal and can damage the cervical mucus thereby impairing fertility. But keep in mind that this factor is rarely considered to be a major culprit in infertility nowadays.

Autoimmune Diseases

Many autoimmune diseases have been associated with infertility primarily through their damaging effects on the ovaries and eggs. Premature ovarian failure and poor ovarian reserve were seen in patients with rheumatoid arthritis, systemic lupus erythromatosis and myasthenia gravis (all are autoimmune diseases).

Genetic Factors

Couples with infertility were noted to have a higher prevalence of genetic and karyotypic (chromosomal) abnormalities (Turner Syndrome, Klinefelter syndrome, Kallmann syndrome, fragile X…) 

Lifestyle Factors

Smoking was associated with both, male and female factors infertility. It was shown to worsen the egg and semen qualities, ovarian reserve, and tubal function.
Obese and underweight women were also at risk of subfertility or even infertility secondary to menstrual irregularities. This weight-fertility association was not very well elucidated in men.
Excessive vigorous exercises were also linked to subfertility. Even though I am a strong advocate for exercise, however strenuous exercise was shown to cause hormonal imbalances that negatively impact the woman’s ovulatory function and thus fertility. Also here, strenuous exercise was not linked to male infertility.
Excessive alcohol consumption was linked to both, male and female factor infertility. However, a moderate alcohol consumption of less than 2 drinks per day was considered acceptable and had no negative effect on fertility. But of course I would advise you to abstain from alcohol whenever planning conception as the safe level of prenatal alcohol consumption has not been established (you can check my article “Plan for your Pregnancy” on https://onlinewomenhealth1.blogspot.com/2020/06/plan-your-pregnancy.html).
The quality of the diet was not linked to neither female nor male factor infertility. The only time where diet was deemed necessary was in patients with Celiac disease (gluten sensitivity), as the latter, if untreated, can cause male and female subfertility which resolves by adopting a gluten-free diet.
Caffeine can be safely consumed up to 2 cups per day.
Environmental factors such as cleaning solvents, heavy metals and pesticides were all linked to infertility, and thus should be avoided in women attempting pregnancy.

What shall you do?

The investigation should be done by an specialist experienced in infertility evaluation and treatment! Although, a less experienced physician can still initiate the infertility workup, however studies have shown that experts in the field were more likely to fulfill the emotional, informational and diagnostic needs of their patients through a more cost-effective plan of care. The general indications for investigation are:

• Healthy women aged less than 35 (without risk factors for infertility) trying to conceive for 12 months
• Healthy women aged 35-40 trying to conceive for 6 months

However, this general rule does not apply to all patients, as some should be investigated immediately upon presentation regardless whether they satisfy the 6 or 12 months period rule. Such patients include:

• Women over the age of 40 years
• Women with irregular menstrual cycles
• Women with absent menstrual cycles
• Women with a history of chemotherapy or radiation therapy
• Women known to have advanced stages endometriosis
• Women with a history of ovarian surgery potentially jeopardizing the ovarian reserve
• Women with known uterine or tubal diseases
• Women whose male partner has a history of groin or testicular surgery, adult mumps, impotence or other sexual dysfunction, chemotherapy and/or radiation
• Women whose male partner has a history of subfertility with another partner
• Women with a history of subfertility in previous relationships

What to Expect in the Fertility Clinic

Choose a fertility specialist who makes you feel comfortable. This applies to all of your medical visits, as studies have shown that patients have better compliance whenever they feel safe, respected and understood by their clinicians.
It is always advisable that you and your partner attend the clinic visit together!
Your infertility specialist is expected to tackle your emotional distress, because infertile couples were shown to have more depression, anxiety, anger and marital discord, so do not feel shy to talk about such feelings.
The first evaluation form included full medical, obstetrical, gynecologic, social, surgical and family histories for both you and your partner.
Your menstrual history is very important as it can hint on whether you naturally ovulate or not, so I would advise you to keep track of your cycles before your clinic visit as this helps your physician to have a stronger idea about your ovulation status.
Also, you and your partner will be interviewed about your sexual habits in order to determine if sexual intercourse is occurring properly for conception.
Then a full physical examination is warranted. Your gynecologist might not examine your male partner, as the latter should be referred to a specialist (Urologist) in case of any suspected male genital pathology.
Your history and physical examination are of utmost value as they will detect the most common causes of infertility.

Then, your physician will order a series of tests. The primary and most important test to be performed is a semen analysis (after 3 days of abstinence). This is an easy, noninvasive test that is essential in any infertility workup to assess male factors.

As for you, a menstrual history can suspect if you are ovulating regularly or not, however sometimes your physician might order certain kits (luteal phase progesterone level or urine luteinizing hormone surge kit) to better assess your ovulatory function.

To evaluate for uterine and tubal factors of infertility, a “hysterosalpingogram” (HSG) can be performed. This is a simple yet bothering procedure during which a contrast material is pushed through your cervix into the uterine cavity, followed by an X-ray image of the uterus. This image can hold useful information on the structural well-being of the uterine cavity as well as the health of your fallopian tubes. Other methods for such an evaluation include a special form of ultrasound called "Hysterosalpingo-contrast Sonography" during which your physician will inject a solution in your uterine cavity and perform an office ultrasound to obtain information on tubal status, the uterine cavity and the ovaries.  If these tests were deemed inconclusive, your doctor might order more invasive tests such as "hysteroscopy" and "laparoscopic chromopertubation" for better assessment of tubal patency (check with a specialist about these options). 

Also, depending on your age and risk factors, an ovarian reserve assessment can be of utmost value as the management plan can differ depending on your ovarian reserve (egg quantity). This can be assessed during your clinic visit by ultrasound, or via certain blood tests (Anti-Mullerian hormone level or day 3 follicule-stimulating hormone and estradiol levels). 

Moreover, your physician might order few other tests, as some hormonal problems can negatively impact your fertility rate (such as thyroid function tests and prolactin hormone level). 

In patients with clinically suspected endometriosis or other pelvic pathologies, a laparoscopic procedure (minimally invasive procedure) can be performed for better diagnosis.

Don’t be overwhelmed, as these tests will be tailored according to your age and infertility risk factors, hence I encourage you again to follow with a specialist in the field who is able to perform the most cost-effective management plan.

Treatment

Once the cause is known, therapy aiming to correct reversible reasons and overcome irreversible etiologies can be instilled.
Lifestyle modification is key, such as smoking cessation, limiting and even abstaining from alcohol consumption, and reducing caffeine intake.
Also, a timed unprotected intercourse is of extreme importance as couples increase their fertility rates by having unprotected sex every one to two days around the expected time of ovulation, or according to an ovulation predictor kit.
Other management plans for male and female infertility can include vitamins, medications, hormonal replacements, surgeries, ovarian stimulation, intrauterine insemination (intrauterine injection of your partner’s concentrated semen) and potentially in-vitro fertilization (IVF). 
The only contraindication to infertility therapy is a contraindication for pregnancy itself (check with your physician).
Finally, a woman’s marital status, sexual orientation and HIV status should NOT preclude any fertility treatment.

 

In conclusion, it is evident by now that infertility is a commonly seen problem, it is associated with many risk factors and most importantly, it is not limited to women, as male factors are seen in 50% of cases of infertility. Lifestyle modifications can help, but seeking the opinion of a professional in the field remains to be the most important step. Don’t lose hope as nowadays most, if not all, infertile couples are able to conceive in one way or another.  

 

Karam