Contents
Functional diagnosis of infertility is a necessary element of endocrine diagnostics. They will be discussed according to frequency of exercise and suitability in clinical practice.
Types of tests used in the diagnosis of functional infertility
1. Test with progesterone
It is one of the basic functional tests in the diagnosis of primary and secondary amenorrhea. For three consecutive days, 50 mg IM progesterone or another progestogen is administered after 5-10 days.
A positive test is the occurrence of bleeding 3-7 days after drug discontinuation – it indicates a normal uterine response and estrogenic test, as well as failure of the luteal phase of the cycle.
A negative test, i.e. no withdrawal bleeding, occurs in pregnancy, in the absence of a uterus, in the absence of the estrogenic reaction of the uterine mucosa (physiologically in the menopause), in the case of gynatresia, i.e. atresia of the genital organs – congenital (most often affects the hymen) or acquired (damaged inflammations, curettage of the uterine cavity).
2. Estrogen-progestogen test (test E)
This test is performed after the exclusion of pregnancy as the next stage of endocrine diagnostics after obtaining a negative progesterone test. For 21 days, a two-phase preparation (phase I – estrogen, phase II – estrogen with progestogen) is administered after or for 21 days estrogen with the addition of a progestogen during the last 10 -12 days.
A positive test – bleeding occurring approximately one week after discontinuation of treatment – excludes the uterine cause of menstrual disorders and raises the suspicion of ovarian failure.
A negative test – no bleeding – indicates that there is a uterine cause of menstrual disorders (e.g. lack of a uterus, Asherman syndrome).
3. Test of stimulation of secretion of gonadotrophins after administration of gonadoliberin (GnRH)
Performing the test is for evaluation purposes. hypothalamic-pituitary-gonadal axis capacity. It is used in the diagnosis of hypogonadotrophic hypogonadism, as well as in the diagnosis of pubertal disorders. Another indication for the test is the assessment of the pituitary reserve. GnRH is administered. iv at a dose of 100 g. It means. gonadotropin concentration: LH, FSH at three time points [before drug administration (time point 0), at 30 and 60 minutes of the test]. In menstruating women, the test is performed during the follicular phase of the cycle or after bleeding is induced with a progestogenic preparation.
The normal stimulation of gonadotropin secretion is a 3-8-fold increase in LH concentration with a peak at 30 minutes and a 3-4-fold increase in FSH concentration with a peak at 60 minutes.
No answer is given in the case of the absence or destruction of the pituitary gland.
Weakened response indicates disturbances in the functions of the hypothalamic-pituitary system or may occur after treatment of pituitary tumors (surgery, radiation).
Disturbance in the proportion of secretion of gonadotrophins:
- an increased stimulation of FSH secretion than LH occurs in anorexia nervosa and in certain disorders of the hypothalamus (the so-called pre-pubertal type of response),
- Overexcitation, mainly in the area of LH secretion, is observed in polycystic ovary syndrome (PCOS).
In patients with lowered estradiol levels and normal gonadotropin levels:
- an increase in the concentration of gonadotropins after administration of GnRH greater than normal indicates damage to the hypothalamus,
- a lower than normal increase in gonadotropin concentration after administration of GnRH indicates damage to the pituitary gland.
4. Clomiphene citrate test
In the course of this test, the antiestrogenic effect of clomiphene (abolition of the negative feedback between estrogens and the hypothalamus) is used. The trial is started on the 5th day of the cycle with the administration of clomiphene citrate (50 mg) for 5 days, and the LH concentration is determined on days 7 and 9. In healthy women, LH secretion is stimulated to the value of 40-80 IU / l. The lack of an increase in the concentration of gonadotropins indicates their deficiency related to pituitary or hypothalamic dysfunction.
5. Short and classic dexamethasone inhibition test
Brief dexamethasone inhibition test (Night Dexamethasone Inhibition Test) is a simple screening test for the diagnosis of hypercortisolemia. Suppressing the serum cortisol concentration below 1,8 µg / dl the next day at 8.00 am, following the administration of the previous evening drug (dexamethasone 1 mg at 23.00 p.m.), allows the exclusion of hypercortisolism. The usefulness of this test for the evaluation of the cause of hyperandrogenism is low due to the too long half-life of DHEAS (T1 / 2. 10-20 hours). Only the performance of this test to assess the cause of hyperandrogenism is small due to the too long half-life of DHEAS (T1 / 2 – 10-20 hours). Only the performance of the classic dexamethasone inhibition test serves not only to exclude or confirm the state of hypercortisolemia (stage I: 0,5 g of dexamethasone every 6 hours for 2 days), but also to differentiate between hypercortisolemia of adrenal origin (ACTH – independent Cushing’s syndrome) and the disease Cushing (stage II: dexamethasone in a dose of 2 g every 6 hours for 2 days), as well as the assessment of the occurrence and possible suppression of hyperandrogenism of adrenal origin measured by the level of DHEAS.
Other forms of ACTH-dependent Cushing’s syndrome (e.g., ecotopic ACTH-producing tumors) may not be sensitive to suppressive doses of dexamethasone. Thus, when analyzing the concentration of adrenal androgens in dexamethasone inhibition tests, the relatively long half-life of DHEAS should be taken into account, hence the evaluation of DHEAS concentration in the short dexamethasone inhibition test is unreliable. This does not apply to DHEA not conjugated to sulfate.
Functional diagnosis of infertility – additional tests
1. Cytogenetic research, necessary in the diagnosis of primary amenorrhea and in the case of suspicion of bodily and gender disorders, rely on the determination of sex chromatin and karyotype. For the determination of sex chromatin, a smear is taken from the oral mucosa. A positive result indicates the presence of at least two X chromosomes in the karyotype of the examined person. The karyotype is determined from peripheral blood lymphocytes.
2. Measurement of morning body temperature. In the ovulatory or two-phase cycle, the body temperature rises by about 0,5 degrees (to about 37 ° C) in 2 days during the periovulatory period. This method is quite unreliable and requires constant observation.
3. Cytohormonal smears. Cytohormonal smears are based on the microscopic assessment of exfoliated vaginal epithelium, the image of which changes depending on the phase of the cycle. In the first phase of the cycle, during estrogenic dominance, surface cells of the vaginal epithelium predominate in the smear. In the second phase of the cycle, progesterone causes the predominance of the cells of the intermediate layer.
4. Histopathological examination of endometrial biopsy. Endometrial biopsy is performed using a Novak probe or a Pipella probe. The test is most often performed in the second phase of the cycle in order to assess the transformation of the uterine mucosa under the influence of hormones.
Other specialist examinations. Depending on the test results obtained, it may be necessary to conduct specialist consultations (including ophthalmological, psychiatric, neurological).
Source: A. Cajdler-Łuba, S. Mikosiński, A. Sobieszczańska-Jabłońska, I. Nadel, I. Salata, A. Lewiński: “FUNCTIONAL DIAGNOSTICS OF HORMONAL DISORDERS WITH ELEMENTS OF DIFFERENTIAL DIAGNOSTICS; Czelej Publishing House