Fertility – Diagnosis, Symptoms, and Treatment

What is Infertility?

Infertility is a medical condition characterized by the inability to conceive after 1 year of regular unprotected intercourse in women under the age of 35, or 6 months of unprotected intercourse in women over the age of 35.  It can be caused by male factors, female factors, or both.  It is most frequently due to female factors such as ovulatory dysfunction, fallopian tube dysfunction, or endometriosis.  Male factors include hypogonadism, medical side effects (e.g., finasteride), testicular varicoceles (dilated veins), or genetic defects in sperm.

Male or female patients can also develop infertility due to pituitary adenoma.  This is a pituitary tumor that results in hypogonadism and breast enlargement in men and menstrual irregularities in women.  Hypogonadism in men can cause symptoms such as breast enlargement, lower energy levels, loss of libido, and erectile dysfunction.

What Causes Infertility?

Infertility is caused by male factors, female factors, or both.  The most common male factors associated with infertility include:

• Low testosterone - hypogonadism
• Post-testicular defects
• Abnormalities of the seminiferous tubules 

Low testosterone levels may be due to the use of medications such as Propecia (finasteride) or Aldactone (spironolactone).  Patients with scrotal varicoceles may also develop infertility – varicoceles are dilated veins in the scrotum that could potentially lead to impaired semen production.  Prior testicular trauma is also a risk factor.  Infectious diseases such as mumps (orchitis) can also lead to testicular failure in some patients.

The most common female factors associated with infertility include:

• Ovulatory dysfunction
• Fallopian tube dysfunction
• Endometriosis 
• Cervical abnormalities

Ovulatory dysfunction can be due to abnormalities in hormone levels. The reproductive hormones in women are much more complex and tightly regulated than those in men, even minor changes can result in infertility. Abnormalities of the fallopian tubes, endometrium, and cervix can all result from abnormalities in these organs at birth or damage from trauma, surgery, or infection. 

Both men and women can potentially develop infertility from thyroid dysfunction (e.g., hypothyroidism) or pituitary tumors (prolactinomas).  Occasionally, no cause of infertility is identified in a couple.

How Common is Infertility?

A large study found that between the years 2006-2010, about 6% of American women between the age of 15-44 experienced infertility.  Other estimates suggest that the prevalence of infertility is approximately 12%-18%.  A study in developed countries demonstrated that female infertility occurs in 37% of cases, male infertility occurs in 8% of cases, and infertility in both occurs in 3% of cases.  An estimated 5% of infertility cases go unexplained.

Signs and Symptoms

The signs and symptoms of infertility vary depending upon the cause. In some cases, there are no signs or symptoms other than the difficulty with conception.

Males with hypogonadism may have low energy, decreased libido, ejaculatory problems, and erectile dysfunction.  They can also have signs of testicular atrophy or loss of pubic hair on physical examination.  Patients with scrotal varices often describe as having a “bag of worms” feeling on palpation of the scrotum.

Women with endometriosis may have irregular menses, pelvic pain, excessive vaginal bleeding during menses (menorrhagia), and pain with sexual intercourse (dyspareunia).

Rarely, male or female infertility is caused by a prolactinoma, a type of pituitary tumor.  This can result in reduced LH and FSH levels, leading to decreased testosterone production by the testes in men, and reduced estrogen production by the ovaries in women.  The pressure from the tumor on the brain may cause headache, nausea, and loss of peripheral vision.  Additionally, men can develop gynecomastia (breast enlargement).

Diagnosis

The assessment of infertility begins by ensuring that you meet the criteria for diagnosis. The inability to conceive for either 1 year (if under the age of 35) or 6 months (if over the age of 35).

Your doctor will commonly order blood tests including a CMP (comprehensive metabolic panel), CBC (complete blood cell count), and thyroid function studies (TSH, free T4).  They will also usually obtain testosterone levels and semen analysis in men.  Women usually undergo an assessment of the uterus and fallopian tubes with hysterosalpingography, hysteroscopy, or ultrasound.  Less commonly, women undergo a minimally invasive surgery known as diagnostic laparoscopy.

More advanced assessment of oocyte quality, ovulation patterns, and genetics are commonly performed if the above-mentioned interventions do not reveal or explain a reason for infertility.  

Fertility Medications and Treatment

The treatment of infertility initially aims to reverse any known underlying causes.  Patients are often provided with general lifestyle measures that can be useful such as quitting smoking, decreasing caffeine intake, and reducing alcohol consumption.

Ovarian induction is often used in women with infrequent ovulation (oligoovulation) not caused by ovarian failure.  The most common ovulation induction agents include:

• Clomid (clomiphene)
• Aromatase inhibitors such as Femara(letrozole)
• Pulsatile GnRH or gonadotropin therapy (LH and FSH)

Individuals with fallopian tube obstruction can benefit from tubal reconstruction surgery.  This method is associated with a higher risk of ectopic pregnancy and requires regular monitoring with pregnancy tests while trying to conceive.  In vitro fertilization is another option that is usually preferred in older women or those with significant fallopian tube disease.

Women with infertility due to endometriosis may benefit from surgical resection of the endometriosis, ovulation induction, and intrauterine insemination.  Other conditions that can be surgically corrected include submucous fibroids, endometrial polyps, and septate uterus.  Infertility related to cervical factors can be treated by bypassing the cervix with intrauterine insemination.  This is often done in concert with ovulation induction agents.

References:

1. Practice Committee of American Society for Reproductive Medicine. Diagnostic evaluation of the infertile female: a committee opinion. Fertil Steril 2012; 98:302. - https://www.ncbi.nlm.nih.gov/pubmed/25936238
2. Dancet EA, D'Hooghe TM, van der Veen F, et al. "Patient-centered fertility treatment": what is required? Fertil Steril 2014; 101:924. - https://www.fertstert.org/article/S0015-0282(14)00302-1/pdf
3. ESHRE Task Force on Ethics and Law, including, Dondorp W, de Wert G, et al. Lifestyle-related factors and access to medically assisted reproduction. Hum Reprod 2010; 25:578. - https://www.ncbi.nlm.nih.gov/pubmed/20085914