Causes and diagnosis of infertility in women

fertility test check pregnancy

Infertility is a disease defined as the inability to get pregnant after 12 months or more of unprotected and timed sexual intercourse or therapeutic insemination. In women over 35 or if there is a suspected or known cause of infertility, it is diagnosed after 6 months of failure to achieve a pregnancy.

In a couple, one third of the causes of infertility is due to female factors, one third is caused by male factors and the remaining third is caused by a combination of the two or by unknown causes.

Infertility affects millions of women in the world; it is estimated that 8-12% of couples worldwide are affected by infertility and in developing countries this number could be as high as 50%.

Primary infertility and secondary infertility

The difference between primary and secondary infertility is that in primary infertility the couple has never been able to conceive a child or to deliver a live child, while in secondary infertility the couple has been previously able to give birth but can’t conceive anymore.

Although they are classified distinctly, the causes of both primary and secondary infertility are the same.

Factors affecting fertility in women

Several factors affect female fertility some of which can be corrected to increase the chances of a successful pregnancy.

  1. Age
  2. Timing of intercourse
  3. Duration of the attempts
  4. Body weight
  5. Diet
  6. Previous contraception
  7. Tobacco smoking
  8. Alcohol use
  9. Drugs
  10. Caffeine
  11. Environmental, workplace or home exposures
  12. Stress and anxiety
  13. Sexually transmitted infections (STDs)

Age

One of the most important factors affecting female fertility is age. Women and couples in general used to conceive at an earlier age in the past; in the last decades, due to socio-economic factors such as an increased level of education and higher percentage of working women, the average age of first pregnancy shifted from the early twenties to the early thirties.

The average age of menarche is between 12 and 13 and the best chances to get pregnant are reached at 20-24. Although the average age of menopause is 51, the decline in fertility starts around 24 and chances steeply decline after 37. Aging is associated with a reduced number of eggs (oocytes) as well as reduced quality of the eggs; it is also associated with changes in the uterus and in hormone secretion all of which can influence fertility and complication rates during pregnancy. Moreover, chromosome abnormalities in embryos and fetuses also increase with age: from 23% chance at 30 to 84% chance at 45.

Overall the chances to get pregnant each month range from 25% in the early 20s, to 20% in the early 30s, to 5% in the early 40s.

Timing of intercourse

Sexual intercourse is another important factor affecting fertility and needs to be timed in order to be effective and have chances to conceive. Women are not fertile during all days of the 28 days average menstrual cycle, but only within a 6-day window.

The closer to the ovulation phase of the female partner, the higher the chances of pregnancy. From studies in medical literature, we know that conceiving is possible from 5 days before ovulation up to the day of ovulation. Before or after this timeframe the chances fall to zero.

Duration of the attempts

Duration of the attempts again is an important factor. Not even at peak fertility in the early 20s a properly timed sexual intercourse can guarantee a pregnancy. Chances are estimated to be at most 25% on average in the general population. For this reason, it is important to attempt to conceive each month as the cumulative chance after 6 and 12 months of attempts rises respectively to 75% and 90% at peak fertility and is about 60% after 12 months in the 35-39 age group.

Body Weight

Body weight and body fat percentage, both too high and too low, are responsible for 12% of all female infertility cases. Women who want to increase the chances to conceive should aim for a BMI between 20 and 25.

Diet

A healthy and balanced diet is advised both to maintain a healthy weight and to avoid any nutritional deficiency which could affect fertility. Overall healthy diets have been associated with higher fertility when compared to unhealthy diets.

For what concerns supplements there is low level evidence mostly coming from observational studies and not backed up by randomized trials.

Supplementation with folic acid (Vit. B9) and vitamin B12 might be beneficial not only in the prevention of neural tube defects during the pregnancy but also to increase success of Assisted Reproductive Technology (ART) and have beneficial effects on fertility as well. Excessive supplementation can be harmful too! High levels of vitamin A or retinoids, due to supplementation or absorbed through the skin from cosmetic products, are a known cause of congenital anomalies.

Trans fatty acids seem to be linked to lower fertility, while omega-3 or polyunsaturated fatty acids seem to be linked to higher fertility.

Previous contraception

Previous contraception in the form of intra-uterine device (IUD) and hormonal contraception (oral, transdermal and injectable) and the length of the use of such contraceptive methods has been linked to a slight delay in time to pregnancy, but it is still a topic of debate. The impairment of fertility, when present, is limited to the first months after discontinuation of contraception and overall the chances of pregnancy at 12 months are similar to that of women not using contraception.

Tobacco smoking

Smoking speeds up the loss of eggs leading to an earlier menopause by 1-4 years. Smoking also decreases fertility reducing the chances of conceiving by about 50% and increases the rate of miscarriage and of genetic abnormalities.

Alcohol use

The effects of alcohol during pregnancy are well known and established.

Heavy use and abuse are linked to lower fertility while light and moderate use have no strong association with lower fertility.

Evidence suggests that even moderate use has an effect on Assisted Reproduction Technologies (ART) and alcoholic beverages should be avoided before and during treatments such as IVF.

Drugs

The effects of drugs on fertility have not been clearly established, but both legal drugs such as marijuana and other illicit drugs may disrupt ovulation, increase the risk of pelvic inflammatory disease and the risk of STDs as they are associated with risky sexual behavior.

Caffeine

Moderate intake of caffeine (200mg or 2 cups of coffee per day) appears to be safe during pregnancy and to not decrease fertility when trying to conceive.

Doses above 500mg or 5 cups are associated with a higher risk of miscarriage and lower fertility.

Environmental, workplace or home exposures

There are thousands and thousands of chemicals and not all have been evaluated for their effects on fertility.

Heavy metals, pesticides, herbicides and many more chemicals decrease fertility. Check the Material Safety Data Sheets available online or at your workplace for more information on specific substances.

Stress and Anxiety

Although there is no definitive answer on whether stress and anxiety reduce fertility or not, there are some links between higher stress levels and lower fertility as well as higher stress levels and lower success rate with IVF and assisted reproductive technologies (ART).

Sexually Transmitted Infections (STDs)

Chlamydia and gonorrhea can cause Pelvic Inflammatory Disease (PID) and infertility. They are both preventable by practicing safe sex. Treatment is available for both and effective, but most infections have no symptoms so regular testing is advised for sexually active women with risk factors such as unprotected sex and multiple partners.

Causes of infertility in women

Conceiving and carrying a pregnancy are a natural but pretty complex process where many things can go wrong along the way: hormones secreted in the brain trigger the ovaries first to ripen an oocyte (follicle-stimulating hormone or FSH) and then to release a mature egg (luteinizing hormone or LH); the egg then travels through the fallopian tubes for about 5-7 days and the progesterone level rises to prepare the uterus for implantation; meanwhile the sperm travels from the vagina through the cervix and reaches the fallopian tubes where meets the egg and fertilizes it. Then the fertilized egg starts dividing into more cells and after about 5 days becomes a cluster of cells (blastocyst) and reaches the uterus where it has to attach to the uterine wall for implantation to occur and for the start of the pregnancy.

We will divide the causes in 5 categories and briefly go through the causes of infertility in each one of them:

  1. Oocytes and ovaries issues.
  2. Fallopian tubes issues.
  3. Uterine and cervical issues.
  4. Other issues.
  5. Idiopathic infertility.

Infertility caused by problems with the eggs and/or ovaries

Polycystic ovary syndrome (PCOS) is one of the main causes of infertility in women. Its prevalence is estimated between 4-12% in the worldwide female population. The causes are not yet established but it is thought to be caused by both genetic and environmental factors. Symptoms include metabolic problems such as diabetes and obesity, infertility, irregular or absent menstrual cycles, excessive facial and/or body hair growth, elevated levels of male hormones, cysts filled with fluid inside the ovaries. There are several treatment options available: from lifestyle interventions, to medications, to surgical therapy.

Primary Ovarian Insufficiency (POI) also known as premature ovarian failure describes a condition when ovaries progressively stop producing hormones and releasing eggs before 40, which eventually results in an early menopause. This condition affects about 1% of the female population. There are treatments that target the symptoms arising from POI and conceiving is still possible in 5-10% of the cases, but fertility cannot be restored once eggs stop being released.

Age as already seen is a factor affecting egg quantity and quality. Diet, exposure, weight and all the others mentioned above are all factors that can influence egg quality, quantity and failure of an egg to mature properly.

Endometriosis can affect the ovaries too, with growth of tissue usually found in the uterus, known as endometrium, in other reproductive organs and rarely also other regions of the body. Endometriosis can make it harder to conceive; to treat fertility related issues, surgery or IVF are an option.

Surgery on ovaries or nearby structures, cysts, ovarian cancer, radiotherapy and chemotherapy are other possible causes of infertility due to obstruction or damage to the ovaries and/or the eggs.

Infertility caused by fallopian tubes issues

Blockage or scarring of the fallopian tubes can prevent the eggs from traveling from the ovaries to the uterus, causing infertility.

Endometriosis can cause both blockage and scarring of the fallopian tubes and Pelvic Inflammatory Disease (PID) can cause scarring.

Congenital anatomical malformation, polyps and surgery are other possible causes of scarring or blockage of the fallopian tubes.

Infertility caused by uterine and cervical issues

Fibroids, myomas and polyps are benign (non-cancerous) tumor growths that can cause implantation issues, meaning that the fertilized egg might have troubles to attach to the uterine wall. Fibroids are present in about 20% of women, but in most of them they will not cause problems in conceiving.

Scarring from surgery, infections or trauma, endometriosis and abnormal anatomy of the uterus can also cause implantation issues.

Cervical issues such as narrowing of the cervix due to surgery or scarring from infection or trauma and cervical fibroids might affect the ability of sperm to travel through the cervix and enter the uterus. Narrowing or malformation of the cervix due to congenital causes can also limit the ability of sperm to reach the egg.

The cervix also has glands which normally produce thick and acidic mucus (pH 4,5); before the ovulation the mucus becomes thinner and neutral in pH to allow the sperm to reach the uterus. If such changes don’t happen this can be a cause of infertility.

Infertility caused by other issues

Among some of the other possible causes of infertility there are:

  • Hormonal disorders: thyroid, hypothalamus, pituitary gland, adrenal glands, … can all cause hormonal imbalances and affect fertility.
  • Diabetes and kidney disease can cause menstrual cycle abnormalities and infertility.
  • Autoimmune disorders such as lupus, Hashimoto’s thyroiditis, rheumatoid arthritis may affect fertility too.
  • Medications such as chemotherapy, spironolactone (diuretic), some psychiatric medications can cause abnormal menstrual cycle or infertility.
  • Some genetic syndromes are also a possible cause of infertility.

Idiopathic or unexplained infertility

For 20-25% of couples a definitive cause to explain infertility cannot be identified. In these cases, it is classified as idiopathic or unexplained infertility.

Tests for diagnosing infertility in women

To assess the cause of infertility in females there are several different tests available:

  • Medical consult. The specialist will ask about the family and medical history, symptoms, medications used, possible exposures, lifestyle.
  • Physical examination. A complete physical and gynecological examination is conducted right after the medical consultation.
  • Blood tests. To check hormone levels, micronutrient deficiencies, underlying pathologies or genetic conditions.
  • Home ovulation predictor kits. With a small urine sample, they detect hormonal levels to check for ovulation.
  • Basal Body Temperature (BBT) charting. Checking the temperature every day for months can help understand if and when the ovulation occurs.
  • Sexually transmitted diseases (STDs) tests. To check for chlamydia and gonorrhea.
  • Ultrasound. This can be a pelvic ultrasound done with or without a saline injection into the uterus to assess the anatomy and shape of uterus, fallopian tubes and ovaries. Or it can be a transvaginal ultrasound.
  • Hysterosalpingogram (HSG). An X-Ray with dye injection to check the uterus and fallopian tubes.
  • Endometrial biopsy. To check for pathological changes of the uterine walls.
  • Laparoscopy and hysteroscopy. Known as keyhole surgery, it is a minimally invasive surgical technique that involves small incisions in the lower abdomen to insert a thin instrument with a camera and take a look at the organs and if needed perform surgery.

Treatment options for female infertility

Treatments depend on the cause of infertility and several treatment options are available to address the different causes:

When the above are not indicated or are not able to solve the infertility issue in the woman, there are still other options available to conceive and known as Assisted Reproductive Technologies (ART):

  1. Intra-uterine insemination (IUI) also known as artificial insemination.
  2. In-vitro fertilization (IVF)
  3. IVF with egg donation.
  4. Embryo transfer with donor embryo.
  5. Gestational carrier.
  6. Surrogacy.

We will talk more in detail about all treatment options for female infertility in a dedicated article.

For the causes, factors, diagnosis of infertility in men, check the dedicated article on male infertility.


Sources
  • The BOSTON IVF Handbook of Infertility – Fourth Edition
    SR Bayer, MM Alper, AS Penzias – CRC Press, 2018
  • Fertility and infertility: Definition and epidemiology.
    M Vander Borght, C Wyns – Clinical Biochemistry, Dec 2018
  • Timing of Sexual Intercourse in Relation to Ovulation.
    AJ Wilcox, CR Weinberg, DD Baird – The New England Journal of Medicine, Dec 1995
  • ABC of subfertility – Extent of the problem.
    A Taylor – The British Medical Journal, Aug 2003
  • Diet and Fertility: A Review
    AJ Gaskins, JE Chavarro – American Journal of Obstetrics and Gynecology, Apr 2019
  • Return of fertility after discontinuation of contraception: a systematic review and meta-analysis.
    T Girum, A Wasie – Contraception and Reproductive Medicine Journal, Jul 2018
  • Return to fertility following discontinuation of oral contraceptives.
    KT Barnhart, CA Schreiber – Fertility and Sterility Journal, Mar 2009
  • Primary ovarian insufficiency: an update.
    L Cox, JH Liu – International Journal of Women’s Health, Feb 2014
  • National Institutes of Health (NIH) – US Department of Health & Human Services
  • American Society for Reproductive Medicine

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