Fertility, subfertility and contraception Flashcards
Why do people with PCOS have anovulation/oligoovulation?
Increased androgen production → increased LH secretion → disrupted LH/FSH balance → impaired follicle maturation
What is the difference between ovarian insufficiency and premature menopause?
Insufficiency: IMPAIRED functional capacity
Menopause: complete loss of ovarian function
Why do women with ovarian insufficiency have high FSH and LH?
Impaired follicular development → low oestrogen → loss of inhibition on FSH and LH
What is the definition of primary amenorrhoea?
Absence of menses at the age of 15 or order
What is the definition of secondary amenorrhoea?
Absence of menses for more than 3 months in women with previously regular cycles or 6 months in women with previously irregular cycles
What is the definition of oligomenorrhoea?
Menstrual cycle with intervals of 35-90 days
What is the definition of infertility?
Inability of a couple to conceive despite one year of unprotected sex
When in the menstrual cycle is the onset of pain from PID most common?
During or shortly after menses
How is ovarian insufficiency diagnosed?
Elevated FSH after 3 months of amenorrhoea in a women under 40
What is the only risk factor for ovarian ectopic pregnancies?
Intrauterine devices
What is the strongest predictor of failure of methotrexate therapy for ectopic pregnancy?
HIgh serum hCG
What is the medical treatment regimen for spontaneous abortion?
200mg oral mifepristone followed by 800mcg of misprostol intravaginally
What is the mechanism of mifepristone?
Progesterone antagonist
What is the function of misoprostol?
Prostaglandin E1 analogue
What is the most common cause of miscarriage?
Foetal chromosomal abnormalities (50%)
When can an ectopic pregnancy be managed expectantly?
- Patient in minimal pain
- Decreasing bHCG
- Diagnosis in doubt
What BhCG level is considered safe for medical management of an ectopic pregnancy?
< 5000
Women with a higher hCG are more likely to require multiple courses of MTX therapy or experience treatment failure
What is the main mechanism of the COCP?
Suppression of follicle development and ovulation
- Makes cervical passage more hostile for spermatozoa*
- Blocks implantation by altering the endometrial lining*
- Inhibits tubal peristalsis*
- Thickens cervical mucous to form a barrier to sperm*
Which class of drugs reduces the effectiveness of the COCP?
Anticonvulsants
Alternative options or higher doses should be considered
What is the efficacy of levonorgestrel emergency contraception?
89% if taken within 72 hours
What is the efficacy of ulipristal (selective progesterone receptor modular) as emergency contraception?
90% if taken within 5 days
What is the mechanism of clomiphene citrate?
Inhibits hypothalamic estrogen receptors → blocks normal negative feedback of estrogen → increased pulsatile secretion of GnRH → increased LH and FSH
How is anovulation diagnosed?
No rise in serum progesterone 7 days before onset of menses
Progesteone should rise shortly after ovulation
How are uterine and tubal abnormalities screened?
Hysterosalpingography
Given the woman has no history of pelvic infections, endometriosis or ectopic pregnancy
How is sex hormone binding globulin affected by PCOS?
Increased insulin → decreased hepatic synthesis of SHBG → elevated free androgen → hyperandrogenism
How is PCOS diagnosed?
2/3 of the following:
Hyperandrogenism
Oligo- and/or anovulation
Polycystic ovaries on ultrasound
What is the most common site of involvement in endometriosis?
Ovary
Endometriosis located at the { } will present as pain with defectation
Pouch of Douglas
What is the most important risk factor for ectopic pregnancy?
Anatomic alteration to the fallopian tubes
E.g. PID, endometriosis, surgery, previous ectopic
What is the definition of infertility?
Inability to convieve after 12 months of unprotected sex for women < 35 and 6 months in women > 35
What is the definiton of primary infertility?
The couple has never been able to concieve
What is secondary infertility?
The couple meets the definition of infertility but has conceived before
How is ovarian reserve assessed?
Day 3 FSH and estradiol levels
AMH levels
What is the usefulness of measuring a woman’s anti-mullerian hormone levels?
Marker of ovarian reserve
Expressed by small preatral and early antral follicles
Reflects the size of the primordial follicle pool
Levels decline as the primordial follicle pool declines with age until it is undetectable at menopause
Why might spironolactone be given to a woman with PCOS?
Antiandrogenic properties
Competes with dihydrotestosterone (pre-testosterone) for binding to the androgen receptor and inhibits enzymes involved in androgen biosynthesis
How are chocolate cysts formed?
Cystic bleeding (menstruation) of the ectopic endometrial tissue results in cysts filled with blood that have a chocolate appearance
What is the aetiology of increased serum testosterone in a woman with PCOS?
Increased estrogen → increased LH → theca cell stimulation → increased androgen production
Increased LH relative to FSH → decreased conversion of testosterone to oestrogen
PCOS is a risk factor for which cancer?
Endometrial
Increased oestrogen
When in their cycle are females fertile?
Ovulation and the 5-6 days prior (sperm can survive 5 days)
Why might short cycles impair a woman’s ability to conceive?
Shortened follicular phase → impaired follicular development
When is letrozole used for infertility?
Aromatase inhibitor
Used in PCOS
→ decreases testosterone → decreases oestrogen → no suppression of FSH → follicle development
How does metformin improve fertility in women with PCOS?
Decreased insulin → decreased androgen → decreased oestrogen → reduced suppression of FSH → follicle development
Why does endometriosis cause infertility?
Shedding of endometrial tissue in the adenexae → inflammation → scarring
What is a normal sperm count? (sperm/mL)
15 million
Why does hyperprolactinaemia cause infertility?
Prolactin inhibits GnRH release
What is idiopathic dysspermatogenesis?
Abnormalities in sperm number, morphology and/or motility with no identifiable cause
Most common primary testicular defect
What is the genetic abnormality in Klinefelter syndrome?
XXY
Impaired spermatogenesis + low testosterone + small testes → infertility
Name 3 causes of aquired testicular defects which may cause male infertility
- Varicocele (pampiniform plexus dilation)
- Infection (germinal cell damage)
- Radiation
- Chemotherapy + hormonal therapy
- Anti-sperm antibodies
Name 3 sperm transport disorders which may lead to male infertility
- Bilateral vas deferens obstruction
- Primary ciliary dyskinesia
- Retrograde ejaculation (failure of bladder sphincter)
- Erectile dysfunction/premature ejaculation
How is fertility 2o to a prolactin adenoma treated?
Dopamine agonist therapy (cabergoline)
Dopamine inhibits prolactin secretion from the anterior pituitary
Name 2 assisted reproductive technologies
- Intrauterine insemination (IUI) - gives the sperm a “head-start”
- In-vitro fertilisation
- IVF with intracytoplasmic sperm injection
How does increased insulin lead to hyperandrogenism?
- Stimulates theca cells
- Decreased hepatic sythesis of SHBG
What is the traditional regimen for starting contraception (OCPs, vaginal rings, implants, Depo)?
Start during menses
Excludes pregnancy and contraception is effective immediately
If a patient is sick (e.g., vomiting, diarrhoea) while on the pill, how long until they are protected again?
7 days
Of levonorgestrel, ulipristal and the copper IUD, which is the most effective emergency contraception?
Copper IUD
For it to be effective, how long can you wait after unprotected sex to have a copper IUD?
5 days
Or up to day 12 of the menstrual cycle because of intertility before this point
What is the main MoA of the Depo injection, Mirena and Implanon?
Prevention of ovulation
How should breakthrough bleeding on continuous contraception methods be managed?
3-4 day hormone-free intervals
Which contraceptive methods are most associated with a worsening of acne?
Progestin-only
Amenorrhoea is most associated with which contraceptives?
Mirena
Implanon
Depo-Provera
Heavy menses are most strongly associated with which contraceptive methods?
Depo-Provera
Implanon
Decreased libido is most associated with which contraceptives?
Very low-dose combined oral contraceptives
Hirsutism is most strongly associated with which contraceptives?
Progestin-only
Increased vaginal discharge is most associated with which contraceptive?
Vaginal ring (Nuvaring)
All contraceptives can have this effect, however
Weight gain is most strongly associated with which contraception?
Depo-Provera
(20% of women)
Which contraceptives should be avoided in women who are breastfeeding and less than 6 months postpartum?
COCs
Nuvaring
For how long following birth is the OCP contraindicated?
6 weeks
When is smoking a contraindication for the OCP?
Smoker (>15 cigarettes per day) over the age of 35
What blood pressure is a contraindication to the OCP?
SBP > 160 mmHg
OR
DBP > 100 mmHg
In women who do not breastfeed, how long postpartum does ovulation resume?
Mean: 39 days (~6 weeks)
In women who breastfeed, when does ovulation resume?
27-38 weeks
(around 7-9 months)
When can an IUD be inserted after delivery?
Within 48 hours, otherwise 28 days
What endometrial thickness suggests a complete abortion?
<15mm
What is a subchorionic haematoma?
Haematoma formed between the chorion and uterine wall
Caused by separation of the endometrium from the chorion
Risks: miscarriage, stillbirth, preterm labour
What is the incidence of gestastional trophoblastic neoplasia following a hydatidiform mole?
Complete: 15-20%
Partial: 1-5%
What are some of the common symptoms associated with pelvic inflammatory disease, which you must ask about in a history?
Pelvic or lower abdominal pain usually bilateral
Deep dyspareunia
Dysmenorrhoea
Abnormal or increased vaginal discharge
Fever
What are the features of Fitz-Hugh-Curtis syndrome?
Perihepatitis (RUQ pain)
Complication of PID
Which organism causes syphilis?
Treponema pallidum
What is the treatment for syphilis?
Benzathine penicillin
What is the Jarisch-Herxheimer reaction?
A reaction sometimes seen following treatment of syphilis. It is thought to be due to the release of endotoxins following bacterial death.
What are the clinical features of the Jarisch-Herxheimer reaction?
Flu-like symptoms: fever, chills, headache, myalgia
Tachypnea, hypotension, and tachycardia
Exanthem
What is considered frequent enough sexual intercourse in order to have a good chance of conceiving?
Every 2-3 days
What blood tests would you order when investigating female infertility?
Mid-luteal progesterone
Prolactin
Androgens
FSH
Oestrogen
TSH
What are the normal parameters in semen analysis?
Volume: >1.5mL
Count: >15 million/mL
Morphology: >4% normal forms
Vitality: > 58% live
What are the most important risks associated with clomiphene use?
Multiple prenancy
Ovarian hyperstimulation syndrome
What is intracytoplasmic sperm injection (ICSI)?
Advanced form of IVF where one sperm is directly injected into the egg
What is ovarian hyperstimulation syndrome?
Fertility treatments → ovarian hyperstimulation → increased vascular permeability → third space fluid loss, mainly to the abdominal cavity
→ thromboembolic events e.g. stroke
What weeks of gestation make up the second trimester?
13-27 weeks
What weeks of gestation make up the third trimester?
28-40 weeks
After how many miscarriages would you start to investigate the cause of miscarriage?
3
What further tests can be performed for a couple who have had recurrent (more than 3 consecutive) miscarriages?
Sonohysterography for assessment of uterine abnormalities
Anticardiolipin antibody (IgG and IgM) titer and lupus anticoagulant performed twice, six to eight weeks apart
Thyroid stimulating hormone (TSH) and thyroid peroxidase antibodies
Parental karyotype and karyotype of the abortus if the above examinations are normal.
What investigation is used to assess tube patency in an infertile woman?
Hysterosalpingogram
Intra-uterine x-ray
Why isn’t exogenous testosterone used in hypogonadic infertile patients?
Spermatogenesis requires some level of intratesticular testosterone
Exogenous testosterone inhibits LH and therefore intratesticular testosterone
A unilateral or bilateral absence of the vas deferens could suggest which condition?
Cystic fibrosis
Testing for CFTR gene mutation is indicated
Can vasectomies be reversed?
Yes
But less likely with time from surgery
What is the mechanism of action of the copper IUD?
Mild foreign body reaction in endometrium → toxic to sperm and alters sperm motility
What is the most common site for an ectopic pregnancy?
Ampulla of the fallopian tube (70%)
What is the most common cause of male infertility?
Varicocele
When do OCPs become effective?
Immediate if initiated on day 1-5 of the menstrual cycle
Otherwise combined require 7 days and progesterone-only 3 days
When do the implanon and mirena become effective?
Immediate if day 1-5 of menstrual cycle
Otherwise 7 days
For which cancers is the COCP a risk factor?
Breast
Cervical
For which cancers is the COCP protective?
Endometrial
Ovarian
How can a missed miscarriage be medically managed?
Intravaginal misoprostol
(mifepristone is not needed as progesterone levels are already low)
