Anovulation - Clinicals, Diagnosis, and Management

Sexual and Reproductive Health

Clinicals - History

Fact Explanation
History of subfertility Ovulation is an essential factor needed for the fertility. Matured ovum is released with the ovulation which usually occurs nearly 14 days prior to the onset of menstruation. Anovulation or the absence of the ovulation is a major factor contributing to the subfertility. Normal ovulation is controlled by the hypothalamo pituitary ovarian axis where the secretion of gonadotrophin releasing hormone by hypothalamus acts on the anterior pituitary to release follicular stimulating hormone and luteinizing hormone. This FSH and LH act on the ovary inducing the follicular maturation and release of oestrogen. Anovulation may be due to the problems at various levels of this axis such as hypothalamus, pituitary and ovary. Commonest cause of anovulation is polycystic ovarian disease which is a heterogenous multifactorial condition. Polycystic ovarian disease is diagnosed with the presence of 2 out of 3 criteria: Amenorrhoea/oligomenorrhoea, hyperandrogenism and polycystic ovaries on ultrasound scan. History of subfertility
Ovulation is an essential factor needed for the fertility. Matured ovum is released with the ovulation which usually occurs nearly 14 days prior to the onset of menstruation. Anovulation or the absence of the ovulation is a major factor contributing to the subfertility. Normal ovulation is controlled by the hypothalamo pituitary ovarian axis where the secretion of gonadotrophin releasing hormone by hypothalamus acts on the anterior pituitary to release follicular stimulating hormone and luteinizing hormone. This FSH and LH act on the ovary inducing the follicular maturation and release of oestrogen. Anovulation may be due to the problems at various levels of this axis such as hypothalamus, pituitary and ovary. Commonest cause of anovulation is polycystic ovarian disease which is a heterogenous multifactorial condition. Polycystic ovarian disease is diagnosed with the presence of 2 out of 3 criteria: Amenorrhoea/oligomenorrhoea, hyperandrogenism and polycystic ovaries on ultrasound scan.
History of irregular menstruation Usually ovulatory cycles are associated with regular monthly bleeding. Ovulation may also be indicated by mid cycle pain. Irregular bleeding is a feature of PCOD. There is either oligomenorrhoea (cycle duration more than 35 days ) or amenorrhoea (absence of menstruation). History of irregular menstruation
Usually ovulatory cycles are associated with regular monthly bleeding. Ovulation may also be indicated by mid cycle pain. Irregular bleeding is a feature of PCOD. There is either oligomenorrhoea (cycle duration more than 35 days ) or amenorrhoea (absence of menstruation).
Polyuria and polydipsia Insulin resistance causing diabetes mellitus is a feature of PCOD which may be due to defect in insulin receptors. Polyuria and polydipsia
Insulin resistance causing diabetes mellitus is a feature of PCOD which may be due to defect in insulin receptors.
History of hypertension and heart disease PCOD increase the risk of these metabolic complications. History of hypertension and heart disease
PCOD increase the risk of these metabolic complications.
Excessive body hair growth Hirsuitism is a complication due to hyperandrogenism. Excessive body hair growth
Hirsuitism is a complication due to hyperandrogenism.
History of infection, autoimmune disorders, surgery or radiotherapy related/ affects the ovaries These can cause premature ovarian failure. History of infection, autoimmune disorders, surgery or radiotherapy related/ affects the ovaries
These can cause premature ovarian failure.
Vaginal dryness, night sweats, or hot flushes Vaginal dryness, night sweats, or hot flushes are seen in premature ovarian failure associate with low oestrogen levels. Vaginal dryness, night sweats, or hot flushes
Vaginal dryness, night sweats, or hot flushes are seen in premature ovarian failure associate with low oestrogen levels.

Clinicals - Examination

Fact Explanation
Obesity High body mass index is found in patients with PCOD. Obesity
High body mass index is found in patients with PCOD.
Acne, hirsuitism (excessive body hair) and alopecia Features of hyperandrogenism are due to the hypersecretion of androgens by the theca cells in the ovaries due to the stimulation of LH. Acne, hirsuitism (excessive body hair) and alopecia
Features of hyperandrogenism are due to the hypersecretion of androgens by the theca cells in the ovaries due to the stimulation of LH.
Acanthosis nigricans Insulin resistance is a feature of PCOD which may be due to defect in insulin receptors. Acanthosis negricans is the skin lesions characterized by velvety, brownish-black pigmentation of the skin of the posterior aspect of the neck, axillae, elbows and knees. Acanthosis nigricans
Insulin resistance is a feature of PCOD which may be due to defect in insulin receptors. Acanthosis negricans is the skin lesions characterized by velvety, brownish-black pigmentation of the skin of the posterior aspect of the neck, axillae, elbows and knees.
Wide carrying angle, shield chest, low hair line, short stature etc. Turner’s syndrome is a recognized cause of ovarian dysfunction. Wide carrying angle, shield chest, low hair line, short stature etc.
Turner’s syndrome is a recognized cause of ovarian dysfunction.

Investigations - Diagnosis

Fact Explanation
LH and FSH levels LH:FSH ratio is usually increaed (LH/FSH ratio >2:1) in polycystic ovarian disease. FSH level is usually > 40 mUI/mL in premature ovarian failure. LH and FSH levels
LH:FSH ratio is usually increaed (LH/FSH ratio >2:1) in polycystic ovarian disease. FSH level is usually > 40 mUI/mL in premature ovarian failure.
Day 21 day progesterone levels This is done on day 21 of menstrual cycle. Usually progesterone are elevated in the luteal phase of the cycle following ovulation. Estradiol (E2)level would be < 40 pg/mL in premature ovarian failure. Day 21 day progesterone levels
This is done on day 21 of menstrual cycle. Usually progesterone are elevated in the luteal phase of the cycle following ovulation. Estradiol (E2)level would be < 40 pg/mL in premature ovarian failure.
Anti- Mullerian hormone (AMH) This is a new diagnostic method for premature ovarian failure. It is produced by antral follicles and secretion is decreased in these patients. Anti- Mullerian hormone (AMH)
This is a new diagnostic method for premature ovarian failure. It is produced by antral follicles and secretion is decreased in these patients.
Ultrasound scan For the diagnosis of PCOD, 12 or more antral follicles in one ovary and volume of ovary more than 10 ml is a useful criteria. Ultrasound scan
For the diagnosis of PCOD, 12 or more antral follicles in one ovary and volume of ovary more than 10 ml is a useful criteria.

Investigations - Management

Fact Explanation
Ultrasound scan For the follow up of PCOD, and in people with subfertility. Ultrasound scan
For the follow up of PCOD, and in people with subfertility.
Androgen levels: dyhydroepiandrosterone sulfate, androstendione and sex hormone binding globulin To evaluate the hyperandrogenism. Androgen levels: dyhydroepiandrosterone sulfate, androstendione and sex hormone binding globulin
To evaluate the hyperandrogenism.
Serum prolactin level May be needed in hyperprolacinaemia. Serum prolactin level
May be needed in hyperprolacinaemia.
Fasting blood sugar/HbA1c To check the glycaemic state as there can be associated diabetes mellitus in PCOD. Fasting blood sugar/HbA1c
To check the glycaemic state as there can be associated diabetes mellitus in PCOD.
Serum prolactin level Elevated prolactin is seen in hyperprolacinaemia. Serum prolactin level
Elevated prolactin is seen in hyperprolacinaemia.
Anti-adrenal, anti-ovarian and anti-thyroid autoantibodies Important to diagnose the immune system deficiency leading to premature ovarian failure. Anti-adrenal, anti-ovarian and anti-thyroid autoantibodies
Important to diagnose the immune system deficiency leading to premature ovarian failure.
Karyotyping Important to exclude major genetic causes. Karyotyping
Important to exclude major genetic causes.
Thyroid stimulating hormone-TSH Hypothyroidism may be a cause for the anovulation. Thyroid stimulating hormone-TSH
Hypothyroidism may be a cause for the anovulation.

Management - Supportive

Fact Explanation
Management of PCOD with weight reduction First step is weight reduction which itself may be a factor for improving the fertility. Other complications such as menstrual irregularities, subfertility, insulin resistance, hyperandrogenism and other metabolic disorders need specific management. Management of PCOD with weight reduction
First step is weight reduction which itself may be a factor for improving the fertility. Other complications such as menstrual irregularities, subfertility, insulin resistance, hyperandrogenism and other metabolic disorders need specific management.
Psychological support Patients may be suffering from problems such as subfertllity, that may need psuchological support. Psychological support
Patients may be suffering from problems such as subfertllity, that may need psuchological support.

Management - Specific

Fact Explanation
Management of subfertility Ovulation can be induced with various methods. Clomiphine citrate, FSH, and ovarian drilling are the some methods used for ovulation induction. Clomiphine usually starts with a dose of 5omg from day 2-6 of menstrual cycle, after that day 12 scan is performed to see the size of the matured follicle. HCG injection is later given. FSH can be used further for a improved response. Human menopausal gonadotropin (HMG) and FSH can be used to induce ovulation if clomiphene and/or metformin therapy fails. Drilling is a procedure done laparoscopically. Intrauterine insemination (IUI) cycles, and in vitro fertilization (IVF) cycles are particularly useful in people with ovarian failure. Management of subfertility
Ovulation can be induced with various methods. Clomiphine citrate, FSH, and ovarian drilling are the some methods used for ovulation induction. Clomiphine usually starts with a dose of 5omg from day 2-6 of menstrual cycle, after that day 12 scan is performed to see the size of the matured follicle. HCG injection is later given. FSH can be used further for a improved response. Human menopausal gonadotropin (HMG) and FSH can be used to induce ovulation if clomiphene and/or metformin therapy fails. Drilling is a procedure done laparoscopically. Intrauterine insemination (IUI) cycles, and in vitro fertilization (IVF) cycles are particularly useful in people with ovarian failure.
Menstrual regulation Usually ovulatory cycles are associated with regular monthly bleeding. Ovulation may also be indicated by mid cycle pain. Irregular bleeding is a feature of PCOD. There is either oligomenorrhoea (cycle duration more than 35 days ) or amenorrhoea (absence of menstruation). Menstrual regulation
Usually ovulatory cycles are associated with regular monthly bleeding. Ovulation may also be indicated by mid cycle pain. Irregular bleeding is a feature of PCOD. There is either oligomenorrhoea (cycle duration more than 35 days ) or amenorrhoea (absence of menstruation).
Management of hyperandrogenism Hyperandrogenism needs treatment with cyprone acetate, Spironolactone , flutamide and finasteride are antiandrogens that decreasing androgen levels. Management of hyperandrogenism
Hyperandrogenism needs treatment with cyprone acetate, Spironolactone , flutamide and finasteride are antiandrogens that decreasing androgen levels.
Medroxyprogesterone acetate Dosage regimen medroxyprogesterone acetate is 5 to 10 mg/day for 10 to 14 days each month. This is used to treat amenorrhea or dysfunctional uterine bleeding in women with PCOS. Medroxyprogesterone acetate
Dosage regimen medroxyprogesterone acetate is 5 to 10 mg/day for 10 to 14 days each month. This is used to treat amenorrhea or dysfunctional uterine bleeding in women with PCOS.
Aromatase inhibitors Letrozole is an aromatase inhibitor usually used for the hormone-responsive breast cancer. It is also useful in treating induction of ovulation in PCOS. Aromatase inhibitors
Letrozole is an aromatase inhibitor usually used for the hormone-responsive breast cancer. It is also useful in treating induction of ovulation in PCOS.
Antidiabetic agents Antidiabetic drugs are used to improve fertility, decrease insulin resistance, and reduce circulating androgen levels. Antidiabetic agents
Antidiabetic drugs are used to improve fertility, decrease insulin resistance, and reduce circulating androgen levels.
The hormone replacement therapy (HRT) This is used for the management for premature ovarian failure patients. Estrogen replacement decrease the risk of osteoporosis and cardiovascular disease. The hormone replacement therapy (HRT)
This is used for the management for premature ovarian failure patients. Estrogen replacement decrease the risk of osteoporosis and cardiovascular disease.
Management of hyperprolactinaemia This is done using prolactin sparing agents like olanzapine, quetiapine, aripiprazole, or clozapine is important in patients taking antipsychotics. Bromocriptine , cabergoline, quinagolide, and amantadine are some common dopamine agonist that correct the prolactin level. Management of hyperprolactinaemia
This is done using prolactin sparing agents like olanzapine, quetiapine, aripiprazole, or clozapine is important in patients taking antipsychotics. Bromocriptine , cabergoline, quinagolide, and amantadine are some common dopamine agonist that correct the prolactin level.

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