Infertility : definition, causes and investigation

Definition

Infertility can be defined as inability of couples to conceive after 1 year or more of trying.

There are few terms under infertility to describe different types of infertility: 1. Resolved infertility - pregnancies that occur after 1 year of trying without medical intervention, 2. Primary infertility - never pregnant, 3. Secondary infertility - failure to conceive after having previously delivered an infant without the use of infertility treatment.

Causes

Causes of infertility can be divided into male and female factors.

Female factors

Causes of female infertility includes disorder of ovulation, tubal disease, uterine/cervical pathology, endometriosis/pelvic adhesion and other pelvic pathology.

Problem with ovulation can be due to several medical conditions, which usually associated with hormonal abnormalities such as PCOS (polycystic ovarian syndrome) , hypothalamic amenorrhea, ovarian failure, hyperprolactinemia (e.g pituitary tumor), hypothyroidism, hyperandrogenism (e.g congenital adrenal hyperplasia, androgen-secreting tumors) and so on. Some medications also can cause anovulation thus affecting fertility. Besides that, problem with ovulation can also occur due to aging and diminished ovarian reserve.

Measurement of mid-luteal progesterone level, urinary luteinizing hormone using home prediction kit, and basal body temperature charting can be used to document whether ovulation occurs or not. If ovulatory dysfunction suspected, measurement of FSH, prolactin, thyroid-stimulating hormone, 17α-hydroxyprogesterone (if hyperandrogenism suspected), and testosterone (if hyperandrogenism suspected) can assist in identification of the etiology. In women older than 35 years old, assessment of ovarian reserve is recommended. The assessment includes: measurement of FSH and estradiol levels on day 3 of the menstrual cycle, clomiphene citrate (Clomid) challenge test, or transvaginal ultrasonography for antral follicle count.

Tubal blockage causing infertility either by preventing fertilization, in which the sperm unable to reach the ovum on time, or, by preventing fertilized ovum to go to uterine cavity for implantation. Uterine/cervical abnormalities also can be associated with infertility such as congenital uterine anomalies, fibroids, and polyps. Transvaginal sonography and hysterosalpingography allow assessment of the tubes, uterus and pelvis. Hysteroscopy might be done if hysterosalpingography reveals intrauterine abnormalities.

Endometriosis, pelvic adhesion and other pelvic pathology should be considered as causes that can lead to infertility and should be investigated after above causes has been rule out. More invasive procedure i.e laparoscopy might be done to diagnose these conditions.

-Male factors-

Causes of male infertility can be divided into: 1. Altered sperm transport, 2.Primary hypogonadism, 3.Secondary hypogonadism, 4.Abnormal spermatogenesis, 5.Idiopathic.

Men with altered/blocked sperm transport commonly presented with low volume of ejaculate or no ejaculate, which can be confirmed by doing a proper sperm analysis (showing low or no volume of semen). This could be due to erection/ejaculation problem or blockage of the sperm transport. Post ejaculatory urinalysis and transrectal ultrasonography may be performed to rule out retrograde ejaculation and ejaculatory duct obstruction respectively. Scrotal ultrasonography also can be helpful in assessing suspected testicular and scrotal abnormalities such as hydrocele and tumor.

Primary hypogonadism (primary testosterone insufficiency) , also referred as testicular failure or dysfunction, can be defined as insufficient production of testosterone due to testicular disorders. Meanwhile, secondary hypogonadism (secondary testosterone insufficiency), also referred as hypothalamic-pituitary dysfunction is defined as insufficient production of testosterone due to disorders of hypothalamus/pituitary gland. Hypogonadism (testosterone insufficiency) is suspected based on abnormal semen analysis (showing severe oligospermia-reduced number of sperm in semen or azoospermia-no sperm in semen). The relationship between serum FSH level , LH and testosterone can help to distinguish between primary and secondary hypogonadism. Measurement of serum prolactin level assists in detecting hyperprolactinemia that also can cause male infertility. Sometimes the level of LH, testosterone and prolactin are normal but only FSH is high or in the upper range of normal. These highly indicate abnormalities in spermatogenesis. However, many men with abnormal spermatogenesis can have a normal FSH level, thus a normal FSH level does not guarantee the presence of intact spermatogenesis.

In such cases where the initial evaluation unable to identify the causes of infertility, further specialized tests such as specialized sperm and semen studies might be recommended if identification of the cause of male infertility will direct the treatment of infertility.

Infertility evaluation

Generally, infertility evaluation should started after 1 year of unprotected intercourse during which pregnancy has not been achieved. Earlier evaluation may be indicated when there is presence of factors suggesting infertility such as history of pelvic inflammatory disease, amenorrhea, tubal surgery and so on. Other indication for earlier evaluation is the female partner is older than 35 years old. This is because fertility rates reduce and spontaneous abortion and chromosomal abnormality increase with advancing maternal age.

Components of infertility evaluation (history, physical examination and investigation)

See More

In-Vitro Fertilization

In-vitro Fertilization - Basic steps in IVF procedure

See More

Infertility

Dysfunctional uterine bleeding : medical treatment

Once all causes of abnormal uterine bleeding (AUB) have been excluded, medication should be considered as the first line treatment. Medication used in the treatment of dysfunctional uterine bleeding can be divided into hormonal and non-hormonal.

     Combined oral contraceptive pills (estrogen component + progesterone component) have been proven to reduce menstrual blood loss in heavy menstrual bleeding. The progesterone component acts by suppressing ovulation, thus inhibits ovarian production of estrogen and progesterone. This leads to absence of hormonal stimulation for endometrial proliferation and eventually this leads to endometrial atrophy. Meanwhile, the estrogen component of the COCP provides support to the endometrial lining of the endometrium to reduce the occurrence of irregular breakthrough bleeding/spotting. However it is contraindicated in certain conditions including history of thrombosis, stroke, uncontrolled hypertension, migraine with aura, coronary arterial disease, liver disease and history of breast cancer. These contraindications are mainly due to the estrogen component. Adverse effects include hormonal systemic effects such as breast tenderness, mood change and fluids retention. Rarely, it causes venous thromboembolism, stroke and coronary artery disease.

     Progesterone-only therapy includes progesterone-only pills, injected progesterone (DMPA) and LNG-IUS. The action is similar to progesterone component in COCP. However, since there is no estrogen component and no support to the endometrial lining, thus irregular breakthrough bleeding/spotting is more likely to occur. Common systemic  effects of progesterone include breast tenderness, weight gain, acne, water retention and headache .These systemic side effects are more prominent in progesterone-only pills and DMPA. However it is mild in LNG-IUS since this device is inserted into the uterus thus it administers high concentration of progesterone directly to the endometrium with only minimal amount of progesterone escaped into the systemic circulation. Other side effects of progesterone-only therapy,which is breakthrough bleeding as mentioned above, post insertion breakthrough bleeding is also common in LNG-IUS, but it is self limiting and it may be up to 6 months duration before it completely resolves. Other side effects of LNG-IUS are risk of expulsion, perforation and pelvic inflammatory disease. The risks of expulsion and perforation is partially operator dependent. Meanwhile, risk of pelvic inflammatory disease is more likely to occur in severely immuno-compromised patient and women with high risk of sexually transmitted infection.

GnRH agonist and Danazol are both proven to be effective in reducing menstrual blood loss. However, they may be used only as a short-term therapy (short-term usage of GnRH agonist pre-operatively), or for cases in which other medical or surgical therapies has failed or contraindicated (long -term usage of GnRH agonist, or Danazol). GnRH agonist is mainly associated with hypo-estrogenic side effects while Danazol is associated with androgenic effects.   

NSAIDs and tranaxemic acid is effective in reducing menstrual blood loss especially in ovulatory  bleeding. Tranaxemic acid is considered as the 1st line treatment for ovulatory dysfunctional uterine bleeding.

See

Dysfunctional uterine bleeding