Infertility is a highly prevalent issue of our times that affects more people than ever before. It is estimated that up to one in six couples may experience some form of infertility and that these rates are on the rise in the near future.

Infertility is a multifactorial clinical entity, meaning in layman’s terms, that it is caused by multiple factors, which contribute each to a different degree per case, ultimately leading to the manifestation of infertility. These factors may be attributed to the male, female or both partners.

Female factor infertility

Infertility in women is the one investigated more thoroughly during ART and is more commonly the primary underlying cause. This is due to the dual contribution of women in human reproduction: women provide the oocyte, which along with the spermatozoon will create the embryo; in addition to providing the site of fertilisation and gestation, namely the uterus and the rest of the internal reproductive organs that receive the developing embryo. Subsequently, abnormalities in any of these factors may lead to infertility.

The most frequent infertility causes in women are:

This category of conditions includes the most frequent causes of female factor infertility, which affect normal ovarian function. Except for infertility, these conditions may also manifest with menstrual disturbances:

  • Polycystic ovary syndrome – PCOS (polycystic ovaries): one of the most common endocrine disorders, PCOS may cause menstrual disturbances and infertility.
  • Premature ovarian insufficiency: also known as ovarian insufficiency or early menopause, or premature ovarian failure is relatively rare but may manifest due to genetic or acquired causes and may lead to cycle disturbances and infertility.

The reproductive functionality of the ovary must be assessed by a specialized Reproductive Gynaecologist. At EmbryoClinic we provide meticulous female fertility assessment, with fertility ultrasound, AMH measurement etc, which assess the suitability of the whole reproductive tract and determine the most appropriate method of assisted reproduction for your particular case (female fertility assessment).

History of inflammation or surgery in the abdominal and pelvic area may lead to the formation of adhesions, leading to fallopian tube obstruction. Fallopian tube patency assessment may be performed via conventional hysterosalpingography or HyFoSy, the latest method of painless salpingography (female fertility assessment). In case of adhesions, minimally invasive fertility surgery may address the underlying cause directly and restore normal anatomy and function (fertility surgery).

A number of different conditions may affect the anatomy and/or functionality of the uterus and potentially impair embryo implantation and growth. These may include:

  • Uterine fibroids: also known as leiomyomas or myomas, are very frequent benign uterine tumours, which, based on their size and location in the uterus, may lead to embryo implantation failure and miscarriage.
  • Adenomyosis: benign condition which entails the development of ectopic endometrial-like tissue (tissue similar to the internal lining of the uterus) within the myometrium, the muscular wall of the uterus. This condition may lead to clinical symptoms of pain, in addition to affecting uterine receptivity to the embryo and its functionality during gestation and delivery. Selected adenomyosis cases may be manageable via surgery (Fertility Surgery).
  • Congenital uterine abnormalities: these are benign variations of the normal uterine anatomy, which are formed during the embryonic stage of development and include multiple types, most frequently bicornuate and septate uterus (uterine septum). These anatomical abnormalities have been associated with embryo implantation impairment and miscarriage. Normal anatomy may be restored via operative hysteroscopy (Fertility Surgery).

This is a common gynaecological condition that may affect up to half of women with infertility. Apart from the irritating clinical endometriosis symptoms, such as cyclical pain, painful urination, defecation and sexual intercourse, endometriosis also has a considerable impact on fertility in multiple ways:

  • Direct impact on ovarian function, with effects on the growth and ultimate follicle size, in addition to the number of available follicles, in case of ovarian endometriosis (endometrioma).
  • Indirect impact on ovarian function, with increase of oxidative stress and pro-inflammatory factors in the ovarian milieu.
  • Impact on salpingeal function, via epithelium function impairment and formation of adhesions, leading to hydrosalpinx development.
  • Impact on sperm function and fertilisation.
  • Impact on embryo implantation, via impairment of vital factors and mechanisms.

Infertility and endometriosis clinical symptoms may be resolved surgically, with minimally invasive fertility surgery (Fertility Surgery).

Hormones regulate many bodily functions, including reproduction. Reproductive hormones, such as FSH, LH oestrogen and progesterone, even thyroid hormones, prolactin and hypothalamic hormones play very important roles in fertility. Meticulous fertility assessment, must necessarily include hormonal assessment as well (female fertility assessment).

Many autoimmune disorders may impact either directly or indirectly, reproductive function and thus fertility. Such conditions include systemic lupus erythematosus, autoimmune Hashimoto thyroiditis, celiac disease etc.

Many genetic and/or congenital factors may, either on their own or combined with acquired factors, lead to infertility. Specific syndromes associated with partial or complete absence or hypoplasia of the reproductive tract (Mayer-Rokitansky-Küster-Hauser Syndrome), or syndromes associated with ovarian dysfunction (Turner Syndrome) or even genetic mutations outside of specific syndromes that may affect fertility.

Milder cases may be managed in the context of basic ART (In Vitro Fertilisation/Intra-Cytoplasmic Sperm Injection (IVF/ICSI)), however, more severe cases may require more advanced options, such as oocyte donation and gestational surrogacy.

As is the case with any other medical condition, infertility may be exacerbated by certain environmental and/or lifestyle factors, such as:

  • Body weight on the extreme ends of the spectrum and associated conditions (obesity, Anorexia nervosa, bulimia etc).
  • Alcohol abuse.
  • Smoking and use of other tobacco products.
  • Substance abuse.
  • Exposure to chemicals, heavy metals, pesticides etc.
  • Frequent exposure to radiation.

Small lifestyle changes may have a large impact on fertility (See Fertility advice), while a non-medical approach may offer an additional boost in the context of fertility treatment (See Holistic approach).

In many cases, fertility is impaired due to another condition or due to the treatment administered for said condition. A well-known example of this is the administration of chemotherapy and/or radiotherapy for the treatment of malignancy, or surgical intervention (removal of the uterus, ovaries etc) which significantly affect fertility. In these cases, it is recommended to consult with a Fertility Clinic or a Reproductive Gynaecologist for available preventive measures, namely oocyte cryopreservation.

Male factor infertility

The male factor may contribute in the clinically apparent infertility up to 50% of all cases and may in fact by the primary etiologic factor in 30% of infertility cases. Therefore, meticulous assessment of the male factor is vital for the success of the couple’s attempts and is an indispensable part of fertility assessment.

Male infertility may manifest with abnormal sperm concentration (oligospermia or worse; azoospermia), motility (asthenospermia), morphology (teratospermia) or a combination of the above (eg oligoasthenospermia). These abnormalities are diagnosed by semen analysis.

Several medical, environmental or lifestyle factors may lead to male infertility:

  • Varicocele: an abnormal enlargement of the testicular veins. It is the most common, reversible cause of male infertility, which may lead to impaired quantity and quality of sperm. Varicocele is easily manageable by a specialized Andrologist.
  • Metabolic disorders, such as diabetes, obesity etc. In the context of their wider effects on bodily functions, such conditions may also affect male fertility.
  • Anatomical abnormalities of the male reproductive tract, be they congenital or acquired may lead to impaired sperm production or flow during ejaculation:
    • Sperm flow obstruction (at any level from the testicle to the urethra).
    • Undescended testicles.
    • Seminiferous tubules defects – abnormalities (associated with trauma, inflammation etc)
  • Hormonal abnormalities, such as low testosterone and other endocrine gland dysfunction, such as the hypothalamus, pituitary, adrenal and/or thyroid gland. (See male hormonal assessment).
  • Genetic abnormalities: Klinefelter syndrome, Kallmann syndrome, Cystic Fibrosis, Y chromosome microdeletions and many other genetic conditions may negatively affect male fertility (see Genetic testing).
  • Benign or malignant tumours of the male reproductive tract or other organs that affect fertility, such as the hypothalamus, pituitary gland, adrenal glands and thyroid gland
  • Lifestyle and personal health factors may have a considerable impact on spermatogenesis and sperm quality. In particular, the following may exert a negative effect:
    • Smoking (even passively).
    • Obesity.
    • Substance abuse (cannabis, cocaine, anabolic steroids).
    • Alcohol abuse.
  • Infections: male urogenital tract infections (epididymitis, orchitis etc), Sexually Transmitted Infections (HIV, gonorrhea, chlamydia etc) and SARS CoV 2 infection (COVID-19) have been shown to dramatically affect sperm quality, leading to abnormal findings during semen analysis.
  • Sexual intercourse dysfunction: even though such issues may be present irrespective of fertility status, they may indicate a common underlying cause, which may affect both sexual function and fertility and thus should be investigated:
    a. Retrograde ejaculation
    b. Erectile dysfunction
    c. Premature ejaculation
    d. Painful intercourse
    e. Psychosexual dysfunction
  • Immunological disorders, such as the presence of anti-sperm antibodies, celiac disease etc
  • Medications: chemotherapy, testosterone replacement therapy, anabolic steroids, certain drugs such as arthritis medications may lead to male fertility impairment.
  • History of pelvic surgery (eg testicular surgery, prostatectomy) and extensive abdominal surgery may lead to infertility, as there is a chance of trauma or functional impairment of the male reproductive system.
  • Several environmental factors may affect spermatogenesis and sperm quality, such as:
    • Exposure to chemicals (pesticides, benzole-based solvents, pigments etc).
    • Exposure to heavy metals (lead etc).
    • Exposure to ionizing radiation and/or radiotherapy.
  • Testicle exposure to increased temperature and/or pressure (seated position for long hours, tight clothing, cycling etc) may affect male fertility.

Targeted lifestyle changes may help you improve your fertility. Find out more at “Healthy fertility habits