Reproductive Endocrinology & Infertility Flashcards
Why is subfertility a better phrase to use than infertility?
Many of the barriers to conception are relative, rather than absolute, and in about 1/4 cases, no cause can be found.
When is a couple considered subfertile?
After they have tried to conceive for at least 12 months, not using any contraception, and having regular intercourse (every 2-3 days). The woman should be under 40 to maximise chances.
What is the background fertility rate of the general population?
80% within 1 year, 90% over 2 years.
Who do we need to investigate for fertilit issues?
Both partners
What are the main titles in causes of female infertility?
Structural or endocrine: Disorders of ovulation Problem of tubes Problem of uterus Problem of cervix
What are the main titles in causes of male infertility?
Structural or endocrine: Disorders of testis and spermatogenesis Disorders of genital tract Disorders of ejaculation Erectie dysfunction
How should we take a history from a woman with suspected subfertility?
Get an idea of general health and lifestyle, including BMI, smoking, drinking, recreational drugs, diet, and exercise.
Why is BMI important in female fertility?
A BMI below 19, or above 30 increases the risk of irrgular/an-ovulation, so chances of conception are much reduced.
Why is smoking important in female fertility?
Impairs fertility as well as increasing the risk of miscarriage, obstetric complications, IUGR, and may have long term effects on the child.
What is the link between fertility and:
a) cocaine?
b) cannabis?
a) cocaine can cause tubal infertility
b) cannabis can impair ovulation
When taking the sexual history in a case of subfertility, what 3 things do you need to cover?
- Frequency - ideally 2-3- times a week
- Prolonged/recureent absences of either partner
- Potential physical problems during intercourse e.g. dyspareunia, inadequate penetration
What previous medical treatments or conditions might result in impaired fertility?
Rx for malignancy (chemo)
Pelvic surgery or radiotherapy
Systemic disease, esp. those affecting the hypothalamic-pituitary axis.
What are the important signs to look for on examination of a woman with suspected subfertility?
- Hirsutism
- Acne
- Pelvic mass
- Signs of sexual difficulty e.g. vaginismus
- Adnexal mass or tenderness
If a either member of a subfertile couple has had children before, what do you need to ask?
- How many conceptions
- How many for each partner, and how many together
- Any previous problems of pregnancy, delivery, or post-partum
How many categories of disorders of ovulation does WHO describe?
4
What are type I ovulation disorders as categorised by WHO?
Give an example
Hypogonadal hypogonadism
Failure of pulsatile gonadotrophin secretion from pituitary.
Rare e.g. post surgery/radiotherapy for pituitary tumour
What are type II ovulation disorders as categorised by WHO?
Give an example
Normogonadotropic anovulation
Most common example is PCOS
What are type III ovulation disorders as categorised by WHO?
Give an example
Hypergonadotropic hypogonadism
Premature ovarian failure
What are type IV ovulation disorders as categorised by WHO?
Give an example
Hyperprolactinaemia with low/normal FSH & LH
Pituitary microadenoma
How do disorders of ovulation causing subfertility usually present?
Amenorrhoea or oligomenorrhoea
Why can tubal factors cause subfertility?
The ovum has to travel from the ovary to the uterine cavity, and be fertilised along the way.
If there is a physical barrier to either transport or fertilisation, the chances of conception are much lower.
What is the most common cause of tubal damage?
Infection.
If acute infection, it’s usually Chlamydia trachomatis.
How does the risk of tubal damage change with each episode of infection?
It roughly doubles each time:
After 1 episode, risk is 8%
After 2, risk is 16%
After 3, risk is 40%
What infection causing tubal damage is seen more and more commonly in the UK, especially in immigrant populations?
Uterine or tubal TB
What conditions, not obgyn, can cause external tubal damage -> subfertility?
How does this occur?
Appendicitis assoc. with peritonitis
Crohn’s disease/UC
Cause peritubal and periovarian adhesions.
What factor can cause tubal damage -> subfertility even in a patient with patent tubes?
Smoking -> decreased cilia motility
What is the major uterine factor causing subfertility?
Submucosal fibroids and congenital abnormalities
Why are uterine factors important in fertility?
Implantation is less likely to occur if the uterine cavity is distorted in some way.
What cervical factors may influence fertility?
Cervical muscus thickening secondary to infection or anti-sperm antibodies.
Cervical mucus is also hostile to sperm after ovulation.
How can we investigate a woman with fertility issues?
Assess ovulation depending on menstrual hx.
Investigate tubal patency.
Investigate cervical factors.
Investigate male partner.
How is ovulation assessed?
Detected with detection of LH surge approx. 24 hours before ovulation.
If ovulation not detected, Ix anovulation with FSH, LH, and oestradiol on day 2/3 of menstruation, serum prolactin and TFTs.
If serum prolactin is raised-> MRI/CT of sella turcica.
Can also visualise the ovaries with Ultrasonography, but this is time consuming.
What 3 methods can we use to investigate tubal patency?
- Hysterosalpingography
- Hysterosonocontrast sonography
- Laparoscopy and dye insufflation
Why do cervical factors not need to be investigated?
There is a lack of established normal criteria.
Modern treatments such as IVF and IU insemination bypass the cervix anyway.
What is the most useful investigation of male fertility?
Semen analysis
What factors are assessed in semen analysis?
Volume Sperm cell count Motility Morphology Liquefaction time WBC count in sample
What might low volumes of semen per ejaculate indicate?
What is a low level?
Androgen deficiency
Under 1ml
What might high volumes of semen per ejaculate indicate?
How much is too high a volume?
Abnormal accessory gland function
Over 4 ml.
What kind of sperm count is associated with subfertility?
Abnormally high i.e. over 200 million/mL
How many sperm should be mobile for a sample to be normal?
60% should have normal motility within one hour
What endocrine assessments should be made in a subfertile male?
FSH
AMH
LH
Prolactin
What is ovarian hyperstimulation syndrome, and what is it a complication of?
Increased release of oestrogens an progesterones as well as other vasoactive substances, causing increased membrane permeability so fluid moves from intravascular compartment.
It’s a complication of IVF, usually caused by gonadotropin or hCG treatment.
What is ovarian reserve testing?
Different tests designed to measure the likely ovarian response to gonadotrophin stimulation in IVF.
What are the 3 ways we can do ovarian reserve testing?
- Total antral follicle count
- Anti-Mullerian hormone
- FSH
Measure around day 3 of menstrual cycle.
What do we need to do for subfertility in a more holistic sense?
Support and reassure the couple.
Stress and pressure can adversely affect relationships and further contribute to fertility issues.
Fertility support groups may be helpful to the couple.
What lifestyle measures can we suggest to help with subfertility?
- Take folic acid in anticipation of pregnancy
- Regular/frequent sexual intercourse
- Alcohol - don’t drink over the recommended limit, and don’t drink when pregnant.
- Reduce/quit smoking
- Ideal BMI is between 19 and 30 - adjust to account for this.
- Can plan intercourse around cycle, but little evidence of effectiveness.
If the male in the partnership is subfertile due to abnormal sperm counts, what management options are there?
- If obstructive cause, surgical correction may be helpful.
- Lifestyle - can inform men that high scrotal temperature can reduce semen quality, but there is little evidence if wearing loose-fitting underwear will help.
If the male in the partnership is subfertile due to disorders of genital tract, what management options are there?
- Offer gonadotrophins if hypogonadotrophic hypogonadism.
- Depending on disorder, surger may be appropriate.
When a woman is subfertile due to hypogonadal hypogonadism/hypothalamic amenorrhoea (Type I ovulation disorders), what Rx can we offer them?
- Lifestlye changes (weight, exercise etc)
- Pulsatile administration of gonadotrophin-releasing hormone or gonadotrophins with leutenising hormine to induce ovulation.
What is PCOS?
Polycystic ovary syndrome is a condition characterised by polycystic ovaries and systemic symptoms causing reproductive, metabolic, and psychological disturbances.
How does PCOS most commonly present?
With a combination of infertility, amenorrhoea, acne, and/or hirsuitism.
Do all women with polycystic ovaries have PCOS?
No - up to a third of women of reproductive age may have polycystic ovaries, but not PCOS.
How common is PCOS?
Thought to affect around 5-15% of women of reproductive age
What are the 4 essential changes in PCOS?
- Excess androgens
- Insulin resistance
- Raised LH levels
- Raised oestrogen levels
When do most patients with PCOS present?
Peri-pubertal period and through mid-20s
What are the symptoms of PCOS?
Oligomenorrhoea In/subfertility Acne Hirsutism Alopecia Obesity/trouble losing weight Sleep apnoea Psychological symptoms.
What are the signs of PCOS?
Hirsutism
Alopecia/male-pattern balding
Obesity
Acanthosis nigricans
How is PCOS diagnosed?
2 out of 3 of Rotterdam criteria providing other causes have been excluded.
What are the Rotterdam criteria?
- Polycystic ovaries (12+ peripheral follicles or ovarian vol over 10cm^3)
- Oligo-ovulation/anovulation
- Clinical/biochemical signs of hyperandrogenism
A pt presents with oligomenorrhoea and subfertility. What are the differentials?
PCOS
Thyroid disorder Hyperprolactinaemia Cushing's Acromegaly Androgen-secreting ovarian or adrenal tumours
A pt presents with oligomenorrhoea and subfertility. What Ix should be done for our top differential?
Bloods - Total testosterone, SHBG, LH, others indicated by presentation e.g. thyroid hormoes.
USS ovaries.
Fasting lipids and fasting glucose/OGTT.
What are the aspects to managing PCOS?
Lifestyle changes
Medical management depending on if woman wishes to conceive
How can PCOS be managed with lifestyle changes?
Weight control
Exercise
Low GI diet
Why is PCOS associated with increased cardiovascular disease risk?
Associated with obesity, dyslipidaemia and insulin resistance
With which cancer is PCOS associated?
Endometrial
Why is PCOS associated with endometrial cancer?
Oligomenorrhoea and amenorrhoea combined with high oestrogen levels cause endometrial hyperplasia which predisposes to endometrial cancer.
How can we prevent endometrial hyperplasia in women with PCOS?
COCP or cyclical progestogen, or IUS.
Is PCOS managed or cured?
Managed - treat the symptoms.
How is PCOS managed in women who are not planning pregnancy?
COCP for menstrual irregularity Metformin for insulin resistance Co-cyprindrol for acne and hirsutism Eflornithin for hirsutism Orlistat for weight loss.
How is PCOS managed in women who are planning pregnancy?
Clomifene induces ovulation, metformin improves pregnancy rates, and laparoscopic ovarian drilling or gonadotrophins if clomifene resistant.
How common is infertility in PCOS?
PCOS is the cause of 75% of women who are infertile due to anovulation.
What are the complications associated with PCOS?
Infertility is the big one. Endometrial hyperplasia and cancer, increased cardiovascular risk factors, increased risk of type 2 diabetes, sleep apnoea. Complications associated with pregnancy.
What are the complications of PCOS associated with pregnancy?
Higher risk of gestational diabetes, preterm birth, and pre-eclampsia.
What is precocious puberty?
The appearance of signs of pubertal development at an abnormally early age.
What age is considered abnormally early for puberty in a girl?
Before age 8
What age is considered abnormally early for puberty in a boy?
Before age 9
Is precocious puberty more likely to be pathological in girls or boys?
Boys - in girls it’s often a benign central process.
Is precocious puberty more common in boys or girls?
Girls - 5-10:1
Do afro-caribbean or caucasian girls enter puberty earlier?
Afro-caribbean
What social factor is thought to be contributing to earlier puberty?
Obesity
How can precocious puberty be classified?
Gonadotrophin-dependant or central, and gonadotrophin-independent or precocious pseudopuberty.
Benign variants also occur.
What is the pathophysiology of central precocious puberty?
Premature activation of hypothalamic-pituitary-gonadal axis usually idiopathic or due to CNS abnormality
What CNS abnormalities can cause precocious puberty?
Tumours
CNS trauma or injury
Hamartomas
Congenital hydrocephalus or arachnoid cysts.
What is the pathophysiology of pseudoprecocious puberty?
Appearance of secondary sexual characteristics due to increased production of female or male hormones occuring independantly of HPG axis.
What can cause gonadotrophin-independent precocious puberty?
Congenital adrenal hyperplasia
HCG-secreting tumours
Other rare genetic syndromes
Testotoxicosis (AD familial male precocious puberty).
What benign forms of precocious puberty are there?
Non-progressive (stabilises then regresses)
Isolated precocious thelarche/pubarche/menarche.
How does precocious puberty present?
Normal pubertal development occurs earlier than expected or compared to school peers.
What in a hx for precocious puberty might make you suspect central pathology?
Headaches
Visual changes
Seizures
What elements of a history are important to get when faced with a child with ?precocious puberty?
CNS symptoms, age and rate of changes, family history, and growth history ideally plotted on a chart.
How should precocious puberty be assessed O/E?
Height and weight (growth chart), Tanner stage, testicular volume, CNS examination, check for specific causes.
What extra step should be done in boys when assessing precocious puberty?
Measure testicular volume
How does testicular volume change in different types of precocious puberty?
It increases with normal puberty and central precocious puberty, but remains prepubertal in most causes of peripheral precocious puberty.
