2.1 Infertility in Women Flashcards
How can temperature be used to monitor ovulation?
- Rise in basal body temperature 1-2 days after LH surge (indicate ovulation)
- Basal body temperature is lower in the proliferative phase:
How can be urinary LH be used to monitor ovulation?
Serum LH levels rise 24 – 36 hours before ovulation:
• Urinary LH (surrogate marker for serum LH) is measured using the ovulation kit
• Can be tested daily from day 10 until positive (coitus is advised 12 – 24 hours after to maximise pregnancy chances)
How can serum progesterone be used to monitor ovulation?
Blood test detects rise in serum progesterone in mid-luteal phase
How can follicular tracking be used to monitor ovulation?
Document the size and growth of ovarian follicles
How can cervical mucus be used to monitor ovulation?
Nature and consistency of the cervical mucus changes cyclically:
• Follicular phase: minimal thick mucus forming a complex mesh in the cervical canal (proliferation of cervical glands)
• Just before ovulation: high quantity thin stringy mucus (Spinnbarkeit) (due to sudden surge in oestrogen)
• After ovulation: thick impenetrable mucus (progesterone alters nature of the mucus)
Fertilisation is the fusion of the sperm (lifespan ____________; lasting up to 5 days depending on the environment) and the oocyte (lifespan ___________):
• Most pregnancies are when coitus occurs within the ________ prior to ovulation
• Oocyte enters the ampulla of the Fallopian tube within ______________ of ovulation → fertilisation occurs within the Fallopian tube
• Fallopian tube holds the fertilised oocyte (zygote) for _________ (allows some time for the endometrium to prepare for implantation of the embryo)
• Embryo enters the uterine cavity ~3 days after ovulation → implantation occurs 1 – 3 days after entry into the uterine cavity
48 – 72 hours;
12 – 24 hours;
3 day interval;
15 – 20 minutes;
~80 hours
What are the female factors causing infertility?
- Female factors include ovarian causes (most common), tubal causes, uterine/vaginal causes, cervical causes (e.g. congenital malformation, surgical trauma → cervical stenosis and inability to produce normal mucus)
- Other factors include chromosomal balanced translocation, endometriosis, and autoimmune causes (antiphospholipid syndrome → increased risk of early pregnancy loss, coeliac disease)
When is anovulation physiological?
re-puberty, pregnancy/lactation, and post-menopause
what does anovulation present with?
irregular menses, oligomenorrhoea, or amenorrhoea
What are the causes of hypogonadotrophic, hypooestrogenic anovulation?
Class I (Hypothalamic Causes)
- Immaturity of HPG axis (usually occurs transiently around the onset of menarche or perimenopausal decline)
- Kallmann syndrome
- Hypothalamic tumours (craniopharyngiomas, metastatic tumours)
- Autoimmune diseases (lymphocytic hypophysitis)
- Infiltrative diseases (sarcoidosis)
- Intense exercise/stress/eating disorders → treat underlying cause
Pituitary causes
- Hyperprolactinaemia
- External damage (Trauma/surgery to the hypothalamic stalk, Radiation to hypothalamic/pituitary area)
- Sheehan’s syndrome (Anterior pituitary infarction after massive postpartum haemorrhage (PPH))
- Pituitary apoplexy (Sudden haemorrhage or impaired blood supply into pituitary gland due to a pituitary adenoma → increased pressure)
What are the causes of normogonadotrophic, normooestrogenic anovulation?
PCOS
What are the causes of hypergonadotrophic, hypooestrogenic anovulation?
- Chromosomal: Turner syndrome (45XO), other X chromosomal deletions / inversions / duplications / translocations, fragile X syndrome
- Autoimmune: Includes SLE, myasthenia gravis
- Iatrogenic: Radiation, chemotherapy, surgery (for ovaries/in pelvic region)
What are the symptoms of hyperprolactinemia?
galactorrhoea, amenorrhoea, subfertility
How does hyperprolactinaemia cause anovulation?
High prolactin → stimulates dopamine → decreases GnRH → decreases FSH/LH → no LH surge → anovulation
What are the symptoms of sheehan’s syndrome or pituitary apoplexy?
adrenal insufficiency (lethargy, anorexia, weight loss, diabetes insipidus, hypothyroidism, Addisonian crisis → giddiness, vomiting, abdominal pain, hypotension, hyponatraemia with hyperkalaemia), hypogonadism (amenorrhoea, lactation failure)
What are the acute symptoms of pituitary apoplexy?
sudden-onset headache behind the eyes or around the temples (most common) associated with N/V, meningitis, bitemporal hemianopia (pressure on optic chiasm), cavernous sinus thrombosis
What is the pathophysiology of PCOS?
- Uncertain mechanism (with genetic component) leading to excessive LH release or hyperinsulinaemia → hyperandrogenic state of ovaries
- Elevated androgen levels cause early development of many small pre-ovulatory follicles → premature luteinisation → maturation arrest at large antral follicular stage (“cysts” are a misnomer) → oligo/anovulation
What are the presentations of PCOS?
Patients with PCOS often present asymptomatically (incidental finding on ultrasound): • Classic triad (remember PcOS): oligomenorrhoea (with anovulatory cycles), polycystic appearance (enlarged ovary with numerous small peripheral follicles in a “string of pearls” distribution on ultrasound), abnormal secondary sexual characteristics (hyperandrogenism → hirsutism, weight gain, acne → secondary to high virilising hormones and low SHBG)
• Metabolic syndrome (diabetes mellitus/insulin resistance) → increased risk of CVD
• Subfertility (due to anovulation
What is the diagnostic criteria for PCOS?
The first thing to do in the diagnosis of PCOS must be the exclusion of other hyperandrogenic causes → then fulfilment of 2 out of 3 of the Rotterdam criteria (diagnosis of exclusion):
- Oligo/anovulation
- Hyperandrogenism: clinical (hirsutism, male pattern alopecia) or biochemical (raised free testosterone levels)
- Polycystic ovary on ultrasound scan
What is the treatment for PCOS?
- Lifestyle modification: First-line treatment (diet, exercise, weight loss)
- Cyclical COCP/ progestestrone: Ensure withdrawal bleed at least once every 3 months to prevent endometrial hyperplasia/cancer → oestrogen reduces androgen levels in the body
- Symptomatic treatment: Medical treatment for acne/hirsutism/alopecia:
• OCP: decrease androgen production
• Spironolactone: blocks androgenic effects on skin (contraindicated in pregnancy/planning conception) - Diabetics screen
When is diabetes screen done in PCOS patients?
- During pregnancy (24 – 28 weeks): gestational DM (GDM)
- Overweight (BMI ≥ 25kg/m2)
- Not overweight but with additional risk factors (age > 40, personal history of GDM, family history of T2DM
What are the medications if patient with PCOS is keen for pregnancy?
- Clomiphene: oral anti-oestrogen medication
* Gonadotrophin/GnRH analogues (e.g. goserelin)
what are endocrine causes of infertility?
- Hormone-producing tumour of the adrenal gland/ovaries
- Cushing’s disease (hypercortisolism)
- Congenital adrenal hyperplasia (CAH)
- Androgen insensitivity syndrome (AIS)
- Poorly controlled thyroid diseases/diabetes mellitus
what are tubal causes (pathologies/ iatrogenic causes of fallopian tubes) that cause infertility?
- tubal disease: prevents sperm from reaching the egg for fertilisation and transport of the embryo into the uterine cavity → causes ectopic tubal pregnancies
- Blockage: Prevents proper transport of the egg and sperm
- hydrosalpinx
- tubal ligation
What is the definition of hydrosalpinx?
Swollen fluid-filled tubes causing obstruction of sperm migration:
• Retrograde flow of tubal contents into the endometrial cavity creates a hostile environment for embryo implantation
• May cause chronic pelvic pain
What are the causes of tubal diseases?
- Pelvic inflammatory disease (PID) caused by Chlamydia trachomatis (most common cause) and Neisseria gonorrhoeae
- Severe endometriosis (see below)
- Iatrogenic causes (history of salpingectomy, ascending infection from uterine instrumentation/IUD insertion, Filshie clip application (for tubal ligation))
- Adhesions from previous surgeries
- Non-tubal infections (e.g. appendicitis, IBS)
- Pelvic TB (rare)
what is the surgical procedure to treat proximal tubal blockages?
Clearing proximal blockages of Fallopian tubes with a cannula via hysteroscopy (examining the interior of uterus with hysteroscope
what is the surgical procedure to treat proximal tubal blockages?
Tubal cannulation: Clearing proximal blockages of Fallopian tubes with a cannula via hysteroscopy (examining the interior of uterus with hysteroscope
what is the surgical procedure to treat distal tubal blockages?
Neosalpingostomy: Surgery to drain and unblock distal tube disease → suture edges to keep the tubes open
what is the surgical procedure to treat hydrosalpinx?
Salpingestomy: of Fallopian tubes (increases success of IVF by 50%)
Infertility may result from impaired implantation of the embryo due to mechanical issues or reduced endometrial receptivity. What are these causes?
Uterine fibroids, Endometrial polyps, endometrial adhesions (Asherman’s syndrome), endometriosis
What is endometriosis?
Endometriosis is the deposition of endometrial tissue outside of the uterus (different from adenomyosis → deposition in the myometrium – still part of the uterus)
Where is endometriosis found?
Commonly found in the pelvis (ovaries, ovarian fossae, uterosacral ligaments, pouch of Douglas) → may range from mild to severe
How does endometriosis decrease fertility?
anatomic distortion (from pelvic adhesions), endometrioma formation (damages ovarian tissue), release of cytokines and growth factors (impede normal ovulation and fertilisation, and implantation)
What are the causes of endometriosis?
- Retrograde menstruation and implantation theory (most widely accepted): endometrial tissue shed is transported via Fallopian tubes into peritoneal cavity → implants on the surfaces of pelvic organs
- Coelomic metaplasia theory: spontaneous metaplastic change in mesothelial cells derived from the coelomic epithelium
- Vascular/lymphatic dissemination of endometrial cells
- Direct transplantation of endometrial tissue
What are the symptons of endometriosis?
- gynaeocological: dysmenorrhoea, non-cyclical pelvic pain, deep dyspareunia, fatigue, infertility
- non gynaecological: dyschezia (constipation associated with defective defecation reflex), dysuria, haematuria, cyclical per-rectal bleeding, shoulder pain
How is the management of pain treated for endometriosis?
- Analgelsia: NSAIDs (ibuprofen, aspirin etc.)
- Hormonal medication (little evidence): COCP, progestogens, LNG-IUS (Mirena®), GnRH agonists
- Surgery: For patients with failed medical management
What are the causes of developmental defects of the Mullerian system (Fallopian tubes, uterus, cervix, upper third of the vagina) may also cause female infertility?
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: very rare embryonic growth failure of the Mullerian duct → agenesis or underdevelopment of vagina, uterus, or both
What are the causes of developmental defects of the Mullerian system (Fallopian tubes, uterus, cervix, upper third of the vagina) may also cause female infertility?
- Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: very rare embryonic growth failure of the Mullerian duct → agenesis or underdevelopment of vagina, uterus, or both
- Lateral fusion defects
- Vertical fusion defects
What kind of lateral fusion defects are the most common?
septate, arcuate, uni/bicornuate uterus, uterus didelphys → double uterus with two separate cervices
What are vertical fusion defects?
Presence of vaginal septum (transverse/longitudinal), cervical agenesis/dysgenesis
