Fertility ? maybe need to finish Flashcards
What is infertility defined as?
The failure to conceive after ONE YEAR or more of frequent, unprotected sexual intercourse.
How many couples are affected by infertility in the UK?
1 in 7 couples
When should couples be referred for infertility?
After trying to conceive for 12 months after frequent (every 2-3 days), unprotected sexual intercourse.
If the woman is >35, when should couples be referred for infertility?
After 6 months
What is 1ary infertility?
Couples who have never conceived
What is 2ary infertility?
Couples who have previously conceived
In males, what is the role of LH?
Acts of Leydig cells within the testes to produce testosterone
What cells does LH act on in males?
Leydig cells
What is the pathway in sperm development?
1) The hypothalamus releases GnRH
2) GnRH acts on anterior pituitary to stimulate release of LH and FSH
3) LH acts on Leydig cells within the testes to produce testosterone
4) Testosterone and FSH interact with Sertoli cells to stimulate sperm development
How does testosterone affect GnRH secretion?
Testosterone also provides negative feedback to the hypothalamus to suppress GnRH secretion.
What are the 4 main causes of infertility?
1) Male factor infertility i.e. sperm proboelms (30%)
2) Ovulation causes (25%)
3) Tubal causes (20%)
4) Uterine/peritoneal causes (10%)
In 40% of affected couples, both male and female infertility factors are responsible for infertility.
What are causes of female factor infertility commonly separated into?
1) Disorders of ovulation
2) Fallopian tube causes
3) Uterine/peritoneal causes
General lifestyle advice for couples trying to get pregnant?
1) The woman should be taking 400mcg folic acid daily
2) Aim for a healthy BMI
3) Avoid smoking and drinking excessive alcohol
4) Reduce stress as this may negatively affect libido and the relationship
5) Aim for intercourse every 2 – 3 days
6) Avoid timing intercourse
7) Men to wear loose-fitting clothing
Is timed intercourse to coincide with ovulation recommended?
No - can lead to increased stress and pressure in the relationship.
What are the 3 main types of ovulatory disorders leading to infertility?
Group I – hypothalamic-pituitary failure
Group II – hypothalamic-pituitary-ovulation dysfunction
Group III – ovarian failure
What occurs in Group I – hypothalamic-pituitary failure?
Hypogonadotropic hypogonadism –> There is a failure to produce the required amount of LH and FSH, resulting in anovulation.
What does group II – hypothalamic-pituitary-ovulation dysfunction occur as a result of?
PCOS
What is the most common cause of female infertility?
PCOS
What does Group III –ovarian failure occur as a result of?
Hypergonadotropic hypogonadism:
There is normal hypothalamic and pituitary function but there are insufficient numbers of follicles within the ovary. Therefore, there is less oestrogen produced and follicles do not develop fully. This results in anovulatory cycles.
Give 3 other ovulatory causes of infertility
1) Sheehan’s syndrome
2) Hyperprolactinaemia
3) Pituitary tumours
What is Sheehan’s syndrome? How can it lead to infertility?
Ischaemic necrosis of the pituitary leads to hypopituitarism.
This can occur as the result of severe hypotension or haemorrhagic shock secondary to massive post-partum haemorrhage.
How can hyperprolactinaemia result in infertility?
This inhibits both FSH and LH secretion and can lead to menstrual dysfunction and galactorrhoea.
How can pituitary tumours lead to infertility?
Pituitary tumours – The tumour displaces or destroys normal pituitary tissue and can affect the production of FSH and LH
What is the most common cause of fallopian tube damage lead to infertility?
PID usually 2ary to chlamydia or gonorrhoea infection
What is the most prevalent uterine or peritoneal cause of infertility?
Endometriosis –> causes inflammation and adhesions in the pelvis that can distort pelvic anatomy
How is male factor infertility diagnosed?
Traditionally, male factor infertility is diagnosed by observing sperm abnormalities during semen analysis.
Semen analysis assesses sperm count, motility, morphology, vitality, concentration and volume.
Define a normal semen analysis:
1) volume
2) semen pH
3) concentration of sperm
4) total number of sperm
5) motility of sperm
6) vitality of sperm
7) % of normal sperm
1) >1.5ml
2) >7.2
3) >15 million per ml
4) >39 million per sample
5) >40% of sperm mobile
6) >58% of sperm active
7) more than 4% of sperm are normal
Define polyspermia (or polyzoospermia)
A high number of sperm in the semen sample (more than 250 million per ml).
Define normospermia (or normozoospermia)
refers to normal characteristics of the sperm in the semen sample.
Define oligospermia (or oligozoospermia)
A reduced number of sperm in the semen sample.
It is classified as:
a) Mild oligospermia (10 to 15 million / ml)
b) Moderate oligospermia (5 to 10 million / ml)
c) Severe oligospermia (less than 5 million / ml)
Define cryptozoospermia
very few sperm in the semen sample (less than 1 million / ml).
Define azoospermia
absence of sperm in the semen
What hormone is necessary for sperm creation?
Testosterone
What 3 categories can male factor infertility be classified into?
1) Obstructive infertility –> a problem with the sperm delivery
2) Non-obstructive infertility –> a problem with the sperm production
3) Coital infertility –> infertility secondary to sexual dysfunction
What is the most common cause of obstructive azoospermia
Previous vasectomy
Give some other causes of obstructive infertility in males
1) Cystic fibrosis
2) Ejaculatory duct obstruction
3) Epididymal obstruction
How can CF lead to obstructive azoospermia?
Congenital absence of the vas deferens
What can cause an ejaculatory duct obstruction?
Previous prostatitis, leading to fibrosis of the ejaculatory duct or by congenital prostatic cysts
What can cause an epididymal obstruction?
STIs –> May occur secondary to a chlamydia or gonorrhoea infection which can cause inflammation and fibrosis of the epididymis
What are some hormonal causes of non-obstructive infertility?
Hypogonadotrophic hypogonadism (low LH and FSH resulting in low testosterone), can be due to:
1) Pathology of the pituitary gland or hypothalamus
2) Suppression due to stress, chronic conditions or hyperprolactinaemia
3) Kallman syndrome
What type of ifnertility can a variocele cause?
Non-obstructive –> associated with impaired testicular function and infertility
Give 3 genetic causes of non-obstructive azoospermia
1) Klinefelter’s syndrome (47, XXY)
2) Androgen insensitivity syndrome
3) Kallmann syndrome
What is the most common genetic disorder associated with infertility?
Klinefelter’s syndrome (47, XXY)
What is the genetic mutation in Klinefelter’s syndrome?
A boy is born with an extra copy of the X chromosome (XXY) –> may adversely affect testicular growth, resulting in smaller than normal testicles, which can lead to lower production of testosterone.
Features of Klinefelter’s syndrome?
- Small testes
- Reduced muscle mass
- Reduced body and facial hair
- Enlarged breast tissue
What happens in androgen insensitivity syndrome?
Child with XY karyotype appearing female due to resistance of the virilising actions of androgens
How can androgen insensitivity syndrome result in non-obstructive infertility?
When there is limited resistance to androgens, there may be poor development of the testes.
What is Kallmann syndrome?
A form of hypogonadotropic hypogonadism.
There is a lack of sex hormone production, resulting in a lack of development of secondary sexual characteristics.
There is also ANOSMIA, and males typically have UNDESCENDED TESTES and a MICROPENIS.
Causes of non-obstructive infertility:
- Hormonal
- Varicocele
- Genetic –> Klinefelter’s syndrome , Androgen insensitivity syndrome, Kallmann syndrome
- Cryptorchidism (undescended testes)
- Previous testicular trauma or damage (e.g. testicular torsion)
- Testicular malignancy
- Sertoli cell only syndrome
- Anorchia (absent testes)
Testicular damage can lead to infertility. What can cause this?
Mumps
Undescended testes
Trauma
Radiotherapy
Chemotherapy
Cancer
What are some causes of coital infertility?
- Erectile dysfunctiuon
- Premature ejaculation (when severe, may occur before vaginal penetration)
- Anejaculation (1ary or 2ary e.g. due to antidepressants)
- Retrograde ejaculation
Couples can have an early referral for infertility investigations, after 6 months of unsuccessful attempts to conceive, if they meet what criteria?
1) The woman is aged 36 years or older
or
2) There is a known cause of infertility
or
3) There is a history of predisposing factors
Initial investigations in male infertility?
1) Semen analysis –> sperm count, motility, morphology, vitality, concentration and volume.
2) Chlamydia screen
Initial investigations in female infertility?
1) Mid-luteal progesterone (day 21 or equivalent in the woman’s cycle) – to assess whether the woman is ovulating
2) FSH and LH to assess ovarian function – poor ovarian function may be indicated by high levels of both FSH and LH
3) Chlamydia screen
4) BMI (low could indicate anovulation, high could indicate PCOS)
Potential further investigations in male infertility?
- Hormone analysis – testosterone, FSH, LH and prolactin
- Genetic testing
- Ultrasound – to investigate any potential structural abnormality
- Testicular biopsy – to both define any histological diagnosis and potentially extract any sperm
- Viral screen – HIV, Hepatitis B and Hepatitis C screening should be offered to those undergoing IVF treatment.
Potential further investigations in female infertility?
Investigations for tubal patency:
- Hysterosalpingogram (HSG)
- Laparoscopy and dye – usually offered when women are known to have a comorbid condition (e.g. endometriosis)
Investigations of the ovarian reserve:
- One of the following should be measured on day 3 of the woman’s cycle to predict the ovarian response to gonadotrophin stimulation in IVF treatment:
1) Total antral follicle count
2) Anti-Mullerian hormone (AMH) (low count= premature ovarian failure)
3) FSH
Viral screen – HIV, Hepatitis B and Hepatitis C screening should be offered for people undergoing IVF treatment.
What does female hormone testing involve in infertility?
1) Serum LH and FSH on day 2 to 5 of the cycle
2) Serum progesterone on day 21 of the cycle (or 7 days before the end of the cycle if not a 28-day cycle).
3) Anti-Mullerian hormone
4) Thyroid function tests when symptoms are suggestive
5) Prolactin when symptoms of galactorrhea or amenorrhoea
When is serum LH and FSH measured in female infertility tests?
Day 2 to 5
When is serum progesterone measured in female infertility tests?
On day 21 of the cycle
(or 7 days before the end of the cycle if not a 28-day cycle).
What is anti mullerian hormone (AMH)?
Is the most accurate marker of ovarian reserve.
Released by granulosa cells in the follicles and falls as the eggs are depleted
What may high FSH indicate in fertility tests?
Poor ovarian reserve (the number of follicles that the woman has left in her ovaries).
The pituitary gland is producing extra FSH in an attempt to stimulate follicular development.
What may high LH indicate in fertility tests?
PCOS
What may a rise in progesterone on day 21 indicate in fertility tests?
indicates that ovulation has occurred, and the corpus luteum has formed and started secreting progesterone.
When can AMH be measured?
Anti-Mullerian hormone can be measured at any time during the cycle
What does a high AMH indicate
A good ovarian reserve
What is a hysterosalpingogram?
A type of scan used to assess the shape of the uterus and the patency of the fallopian tubes.
Purpose of a hysterosalpingogram?
1) Can help with diagnosis
2) Can increase the rate of conception without any other intervention.
Mangement of anovultion for overweight patients with PCOs?
Weight loss - can restore ovulation
1st line pharmacological management to stimulate ovulation?
Clomiphene
What is clomiphene?
An anti-oestrogen drug
How does clomiphene stimulate ovulation?
1) Clomiphene induces ovulation by inhibiting oestrogen from binding in the anterior pituitary.
2) This stops the negative feedback mechanism of oestrogen, thus the secretion of GnRH, FSH and LH increases.
3) This results in greater stimulation of the ovaries and therefore a greater increase in oestrogen production and secretion.
4) The oestrogen stimulates follicle growth and maturation
Other pharmacological management options for female factor infertility?
1) Clomiphene
2) Gonadotrophins
3) Pulsatile GnRH
4) Dopamine agonists
When are dopamine agonists beneficial in female factor infertility?
when the ovulatory disorder is secondary to hyperprolactinaemia
Pharmacological management of male factor infertility?
Gonadotrophins may be given in men with hypogonadotropic hypogonadism
Management of sperm problems?
Surgical sperm retrieval —> used when there is a blockage somewhere along the vas deferens preventing sperm from reaching the ejaculated semen. A needle and syringe is used to collect sperm directly from the epididymis through the scrotum.
Surgical correction of an obstruction in the vas deferens may restore male fertility.
Intra-uterine insemination —> collecting and separating out high-quality sperm, then injecting them directly into the uterus to give them the best chance of success. It is unclear whether this is any better than normal intercourse.
Intracytoplasmic sperm injection (ICSI) —> injecting sperm directly into the cytoplasm of an egg. These fertilised eggs become embryos, and are injected into the uterus of the woman. This is useful when there are significant motility issues, a very low sperm count and other issues with the sperm.
Donor insemination with sperm from a donor is another option for male factor infertility.
What is assisted conception?
Refers to procedures which cause sperm to come into proximity with oocytes to promote conception.
e.g. In vitro fertilisation (IVF)
Complications of assisted conception?
- Ovarian hyperstimulation syndrome (OHSS) – this is a potentially life-threatening complication of superovulation
- Multiple pregnancy
- Ectopic pregnancy
- Pelvic infection
How long is the egg fertile for after ovulation?
24h
How long is sperm fertile within the fallopian tubes for?
<5 days
How soon before the next expected menstrual period does ovulation occur?
12-14 days
When is an earlier referral for investigations in fertility indicated?
- age >36
- known cause or risk factors
- treatment planned that would result in infertility (e.g. chemo)
Lifestyle factors for improving fertility for women?
- folic acid
- vitamin D
- stop smoking
- no alcohol intake
- BMI >19 and <30
- stop recreational drug use
Causes of anovulatory infertility (i.e. hypogonadotropic hypogonadism)?
Also known as WHO Group 1 ovulation disorders
1) Weight loss e.g. anorexia
2) Systemic illness, inflammation e.g. TB, sarcoidosis
3) Pituitary surgery or irradiation
4) Sheehan’s (postpartum pituitary necrosis)
5) Congenital (Kallman’s syndrome)
6) Hyperprolactinaemia
Management of WHO Group I ovulation disorders (Hypogonadotrophic hypogonadism)?
1) Correct weight and underlying health problems
2) Assess eating patterns
3) Moderate exercise
4) Gonadotrophins for ovulation induction, only when health appropriate for the energy demands of a pregnancy
Causes of anovulatory infertility classifications:
Group I: Hypothalamic/pituitary failure
Group II: PCOS (note - this accounts for almost 90% of ovulatory problems)
Group III: Premature ovarian insufficiency
Give 5 causes of hyperandrogenism
1) PCOS
2) Congenital adrenal hyperplasia
3) Cushings
4) Androgen secreting tumour
5) Steroid use
Role of clomiphene?
Medication used to treat infertility in women who do not ovulate, including those with PCOS
Interaction between LH and insulin?
High levels of LH increases insulin resistance
How can hyperprolactinaemia affect fertility?
Can cause infertility
Causes of a mildly raised prolactin (<1000)?
- stress
- recent breast exam
- vaginal exam
- venepuncture
- hypothyroidism
- PCOS
Causes of a moderately raised prolactin (1000-5000)?
- microprolactinoma
- hypothalamic tumour
- PCOS
- antipsychotics
Causes of a severely raised prolactin (>5000)?
Macroprolactinoma
Give 3 causes of pelvic pathology that can cause infertility
1) PID
2) Endometriosis
3) Past abdominal/pelvic infection or surgery (e.g. appendicitis)
Gold standard investigation for pelvic pathology causing infertility?
Laparoscopy
