Fertility and Contraception Flashcards
When can investigation and referral for infertility take place?
When a couple has been trying to conceive without success for 12 months, can be reduced to 6 months if woman is older than 35.
What are common causes of infertility?
Sperm problems Ovulation problems Tubal problems Uterine problems Unexplained
What general lifestyle advice is given to couples trying to get pregnant?
Woman taking 400mcg folic acid daily
Aim for healthy BMI
Avoid smoking and drinking excessive alcohol
Reduce stress - negatively affects libido and relationship
Intercourse every 2-3 days
Avoid timed intercourse
What are the investigations for infertility?
BMI - low = anovulation, high = PCOS
Chlamydia screening
Semen analysis
Female hormone testing:
Serum LH and FSH on day 2-5 of the cycle
Serum progesterone on day 21, or 7 days before end if not a 28-day cycle
Anti-Mullerian hormone
TFTs if symptoms suggestive
Prolactin if galactorrhoea or amenorrhoea
Ultrasound pelvis looks for PCOs or structural abnormalities
Hysterosalpingogram
Laparoscopy and dye test
Semen analysis for male factor infertility
Hormonal testing, genetic testing, transrectal ultrasound, vasography, testicular biopsy
What does high FSH suggest about fertility?
Poor ovarian reserve - the number of follicles left
Pituitary gland is producing extra FSH in an attempt to stimulate follicular development.
What does high LH suggest about fertility?
May suggest polycystic ovarian syndrome.
What does Anti Mullerian hormone suggest about fertility?
Can be measured at any time during the cycle, most accurate marker of ovarian reserve, released by granulosa cells, falls as eggs are depleted
High level means good reserve
What is a hysterosalpingogram?
Assesses shape of uterus and patency of fallopian tubes
Can increase rate of conception without other intervention
Contrast medium injection, can help show tubal obstruction
Risk of infection, prophylactic abx given, screening for chlamydia and gonorrhoea done beforehand
What is the management of anovulation?
Weight loss
Clomifene
Letrozole instead of clomifene - aromatase inhibitor with anti-oestrogen effects
Gonadotropins for those resistant to clomifene
Ovarian drilling
Metformin if insulin resistance and obesity
What is clomifene?
Anti-oestrogen - selective oestrogen receptor modulator
Given daily between days 2-6 of menstrual cycle
Stops negative feedback of oestrogen on hypothalamus, more GnRH release, so more FSH and LH.
How can tubal factors causing infertility be managed?
Tubal cannulation during hysterosalpingogram
Laparoscopy to remove adhesions or endometriosis
IVF
How can sperm problems causing infertility be managed?
Surgical sperm retrieval if there is a blockage - collects directly from epididymis
Surgical correction of obstruction in vas deferens
Intra-uterine insemination - collect and separate high quality sperm then inject into uterus
Intracytoplasmic sperm injection ICSI injected into the cytoplasm of an egg, then injected into uterus of woman.
Donor insemination
How should I assess a man who is concerned about infertility?
Take a full medical, sexual, and social history, including:
Children born to man (with same or different partner).
Length of time trying to conceive.
Frequency and difficulties of sexual intercourse.
Symptoms or history that may suggest primary spermatogenic failure or obstructive, including:
History of mumps, sexually transmitted infections (STIs), or testicular trauma or torsion. Previous urogenital abnormality and treatment (for example undescended testis or orchidopexy). Systemic diseases (for example cardiac failure, chronic renal failure, neoplasia, uncontrolled diabetes, liver cirrhosis, or thyrotoxicosis). Previous surgery (for example hernia repair or orchidopexy).
Ejaculatory or erectile dysfunction.
Drug history.
Details of occupation, for possible exposure to hazards that can reduce fertility (such as pesticides and solvents).
Lifestyle factors - smoking, excessive, or social or occupational situations that may cause testicular hyperthermia.
Physical examination
Examine the penis, check position of urethral meatus, for structural abnormalities.
A scrotal examination may reveal lumps (cancer, varicocele, or hernia); small, soft testes (which may indicate hypogonadism); or undescended testes.
Assess secondary sexual characteristics. In hypogonadism, there may be a decrease in beard and body hair growth and a decrease in muscle mass.
Look for gynaecomastia, which may indicate hypogonadism.
What initial investigations should I arrange in a man to investigate infertility?
Semen analysis - collected after at least 2 days but no more than 7 days of sexual abstinence.
Needs to be complete, report any loss of fraction.
Screen for chlamydia
What is the treatment for an anovulatory cause of infertility?
Controlled ovarian stimulation 1st line - Gonadotrophins are first-line options for patients with hypothalamic amenorrhoea - e.g. Menotrophin
What is infertility?
Not conceiving after trying to have regular (2/3 x a week) unprotected sex for 1 year
What are the main 2 categories to think about when working out what could be reducing female fertility?
What are some other causes?
Ovulatory disorders
Tubal damage
Other - cervical mucus dysfunction, fibroids that distort uterine cavity, previous cervical surgery, chronic debilitating disease
What can cause tubal damage and therefore lead to infertility?
Adhesions: PID and endometriosis
Previous sterilisation
What are the types of ovulatory disorder and what blood results differentiate them?
1 - Hypothalmic pituitary failure
- low gonadotrophins and oestrogen
2 - HPO failure e.g. PCOS (85%)
- Raised LH, low progesterone
3 - Ovarian failure (5%)
- high gonadotrophins, low oestrogen
What are the causes of hypothalamic pituitary failure
Hypothyroid (decreases FSH and LH)
prolactinoma (inhibits GnRH so decreased LH and FSH)
What male factors can lead to infertility?
Genetic dysfunction
Varicocoele (raises testicular temperature)
Testicular cancer treatment Trauma Pituitary dysfunction Hypospadias Erection/ejaculatory failure
What general factors can lead to infertility?
Age
Stress
Obesity Smoking Alcohol Anabolic steroids Recreational drugs Tight fitting clothing
What would you ask in a history of infertility?
Previous pregnancies/fathered any children
Length of time trying
Type of contraception previously used and when stopped Coital freq. Previous STI's, fertility treatment General health - including BMI Drug Hx Female - menstrual Hx, OBGYN hx Male - mumps or measles
When would you request investigations for infertility?
After 1 year of regular intercourse
How would you investigate a female with suspected infertility?
Progesterone on day 21 (Mid-luteal phase)
Oestrogen, LH and FSH on day 2
Chlamydia screen
+/-Thyroid function
+/-Prolactin
How would you investigate a male with suspected infertility?
Semen analysis - masterbation after 2-7 days abstinence of sexual activity
1 abnormal test = repeat
2 abnormal tests = refer
Chlamydia screen
When would you refer someone to secondary care with suspected infertility?
1 year regular intercourse
+ all investigations in primary care come back as normal
What can be done in secondary care to investigate infertility?
Pelvic USS
Tubal patency testing - hysterosalpingography or diagnostic laparoscopy
In depth sperm analysis
How can hypothalamic-pituitary infertility be managed medically?
Gain weight
Reduce exercise
Pulsatile gonadotrophins
Treat hypothyroidism
How can HPO disorder infertility be managed?
Clomifene citrate
+/- metformin
How can hyperprolactinaemia induced infertility be managed?
Dopamine agonist - bromocriptine
How can male hypogonadotrophic hypogonadism be managed?
Gonadotrophins
How does clomifene citrate work?
Anti-oestrogen –> inhibit negative feedback effect that oestrogen has on hypothalamic pituitary axis
What are the ADR’s and CI’s of clomifene citrate?
CI - Ovarian cyst, unexplained vaginal bleed
ADR - hot flush, bloating, head and abdo pain, N&V, breast tenderness, menstrual irregularities
How can infertility be managed surgically?
Tubal catheterisation or cannulation
Surgical ablation and resection of endometriosis
Surgical correction of any epididymal blockage
What are the methods of assisted conception?
Intrauterine insemination
- sperm into uterus
Donor insemination
- donor sperm into uterus
In vitro fertilisation
- retrieve egg and sperm, mix and incubate, put embryo into uterus
Intracytoplasmic sperm injection
- as above but sperm injected directly into egg
Oocyte donation
- IVF but with donor egg
When is donor insemination used?
Man has no sperm
Man has an infectious disease - HIV
Man has a genetic conditions
No male partner
What are the main complications of artificial conception?
Ovarian hyperstimulation syndrome
Ectopic
Pelvic infection
Multiple pregnancy
How does ovarian hyperstimulation present?
Due to fluid loss in third space (mainly abdo):
Bloating
Abdominal pain N&V Diarrhoea Oliguria Ascites SOB
How is ovarian hyperstimulation syndrome managed?
Supportive - fluids and analgesia
DVT prophylaxis
What is the difference between primary and secondary infertility?
Primary is in couples who have never conceived, whereas secondary is in couples who have previously conceived
What are the disorders of ovulation?
I - hypothalamic pituitary failure
II - hypothalamic pituitary ovulation dysfunction
III - ovarian failure
Other ovulatory causes including Sheehan’s, hyperprolactinaemia, pituitary tumours
What is the classification of male factor infertility?
Obstructive - problem with sperm delivery
Non-obstructive - problem with sperm production
Coital infertility - secondary to sexual dysfunction
What are examples of obstructive infertility in men?
Previous vasectomy
Cystic fibrosis
Ejaculatory duct obstruction e.g. previous prostatitis leading to fibrosis
Epididymal obstruction may occur secondary to chlamydia or gonorrhoea
What are causes of non obstructive infertility in men?
Hormonal causes e.g. hypogonadotrophic hypogonadism, hyperprolactinaemia
Varicocoele
Genetic causes e.g. Klinefelter’s, androgen insensitivity, Kallmann
Cryptorchidism - undescended testes
Previous testicular trauma or damage
Testicular malignancy
What are the causes of coital infertility in men?
Errectile dysfunction
Premature ejaculation
Anejaculation
Primary due to psychosexual or neurological causes
Secondary due to previous abdominal/pelvic surgery or certain drugs e.g. SSRIs
Retrograde ejaculation
Penile deformities e.g. Peyronie’s, hypospadias
When is referral for fertility testing available?
One year after frequent unprotected sex
Or early referral after 6 months if
Woman aged over 36, or known cause of infertility, or history of predisposing factors
What initial investigations are available for infertility?
Male - semen analysis assessing sperm count, motility, morphology, vitality, concentration, volume. Chlamydia screen.
Women - Mid luteal progesterone to assess whether woman is ovulating
FSH and LH to assess ovarian function - poor function may be indicated by high FSH and LH
Chlamydia screen
What further investigations in secondary care can be offered for infertility?
Men - hormone analysis; testosterone, FSH, LH, PL
Genetic testing, USS, testicular biopsy, viral screen HIV Hep B and C for IVF
Female - hysterosalpingogram for tubal patency, laparoscopy and dye if e.g. endometriosis
Investigations of ovarian reserve, measured on Day 3 to predict ovarian response to gonadotrophins in IVF
Total antral follicle count
Anti Mullerian hormone - low count = premature ovarian failure
FSH
Viral screen
What are the processes in IVF?
Suppressing natural menstrual cycle Ovarian stimulation Oocyte collection Insemination or intracytoplasmic sperm injection Embryo culture Embryo transfer
How is the natural menstrual cycle suppressed for IVF?
Prevent ovulation
Ensure ovaries respond correctly to gonadotropins
Use of either GnRH agonist or antagonists.
How does GnRH agonist work to suppress natural cycle in IVF?
e.g. goserelin given in luteal phase, around 7 days before expected period
Stimulates pituitary to produce large amount of FSH and LH, then after initial surge there is negative feedback and suppression.
How do GnRH antagonists work to suppress the natural cycle in IVF?
Injections subcutaneously
Daily
e.g. cetrorelix given starting from day 5-6 of ovarian stimulation, suppresses release of LH and ovulation
Means that follicles can be collected that have been developing, but have not been released
How does ovarian stimulation work in IVF?
Subcutaneous injections of FSH starting on day 2 of menstrual cycle for 10-14 days, promotes development of mature follicles
Development closely monitored
When enough developed, to around 18mm in size, FSH stopped and hCG given 36 hours before collection, works similarly to LH and stimulates final maturation
When are embryos transferred in IVF?
Following oocyte collection under guidance of TV scan
sperm and egg mixed in culture medium, or high quality sperm selected and injected, then left in incubator and observed for 2-5 days until they reach blastocyst
Then catheter inserted through cervix into uterus, after 2-5 days highest quality inserted
Pregnancy test after 16 days
When is progesterone administered in IVF?
From oocyte collection to 8-10 weeks gestation, usually as vaginal suppositories
Mimics progesterone usually released from corpus luteum, then placenta will take over
Are any additional scans required following IVF?
USS at 7 weeks to check for fetal heartbeat and rule out miscarriage or ectopic pregnancy, then can proceed with standard care
What are the main complications of IVF?
Failure
Multiple pregnancy
Ectopic pregnancy
Ovarian hyperstimulation syndrome
What are the complications of egg collection for IVF?
Pain, bleeding
Pelvic infection
Damage to bladder or bowel
What is ovarian hyperstimulation syndrome?
Complication of ovarian stimulation during IVF, associated with the use of HCG
What is the pathophysiology of ovarian hyperstimulation syndrome?
Increase in vascular endothelial growth factor released by granulosa cells of the follicles.
Increases vascular permeability, leads to oedema, ascites, hypovolaemia.
Trigger injection of hcg stimulates release of VEGF from follicles.
Activation of RAAS.
What are the risk factors of ovarian hyperstimulation syndrome?
Younger age Lower BMI Raised anti Mullerian hormone Higher antral follicle count Polycystic ovarian syndrome Raised oestrogen levels during ovarian stimulation
How can OHSS be prevented?
Monitor oestrogen and ultrasound to monitor follicles during stimulation with gonadotrophins
Lower doses of gonadotrophins, lower dose of HCG or alternatives
What are the features of OHSS?
Presents within 7 days of hCG injection, late if presents from 10 days onwards
Abdominal pain and bloating Nausea and vomiting Diarrhoea Hypotension Hypovolaemia Ascites Pleural effusions Renal failure Peritonitis from rupturing follicles releasing blood Prothrombotic state so risk of DVT and PE
What is the management of OHSS?
Oral fluids Monitoring urine output Low molecular weight heparin Ascitic fluid removal IV colloids e.g. human albumin solution
Haematocrit may be monitored to assess volume in intravascular space - if goes up, indicates less fluid in space as blood becoming more concentrated
What general advice would you give about taking contraceptive pills?
Doesn’t interfere with intercourse
Easily reversible
No protection against STI’s
May forget to take
How does the COCP work?
Negative feedback suppress FSH and LH surge - stop ovulation
Also thicken cervical mucus and reduce endometrial receptivity to blastocyst
What is the failure rate of the COCP?
9% with typical use - lot lower if used properly
What are the main risks and ADR’s of the COCP?
VTE
Stroke
MI Breast and cervical cancer Breakthrough bleeding Breast tenderness Mood swings
What are the main benefits of the COCP?
Easy to reverse
Relief from menstrual problems
Reduce risk of ovarian, endometrial and colorectal cancer
Reduce risk of benign breast disease and ovarian cysts
Reversible upon stopping
What is the effect of vomiting, diarrhoea or CYP inducing drugs on the efficacy of COCP?
Reduced efficacy
What are the main contraindications for the COCP?
> 35yo + smoking >15/day
Migraine with aura
Uncontrolled hypertension
History of VTE, stroke or IHD
Current breast cancer
Breast feeding <6 weeks post partum
