Subfertility Flashcards
Causes of pre-testicular male subfertility
Hypothalamic disease
- Kallmans
- Prader-Willi
- CHARGE
Pituitary pathology
- Tumours
- Brain injury including iatragenic
Testicular causes of male subfertility
Genetic
- Kleinfelters
- Noonan’s
Cryptorchidism
Acquired
- injury
- varicocele
- tumours
- chemo / radiotherapy
- idiopathic
Post testicular causes of male subfertility
Congenital
- Congenital absence of the vas deferens
- CF
- Youngs
Acquired
- Infection
- Vasectomy
Sperm dysmotility
- Immotile cilia syndrome
- Maturation defects
- Immunological infertility
- Globozoospermia
Sexual dysfunction
For a couple with unexplained subfertility what is the likelihood they will conceive with expectant management?
In unexplained subfertility chances of conceiving with expectant management are high
74% of couples conceive within 12 months
What is WHO Group I ovulation disorder
Ovulation Disorders
WHO Group I : Hypothalamic pituitary failure
Stress, anorexia, exercise induced
What is WHO Group II ovulation disorder
ovulation disorder
WHO Group II :
Hypothalamic-pituitary-ovarian dysfunction
PCOS
What is WHO Group III ovulation disorder
ovulation disorder
WHO Group III : Ovarian failure
What type of ovulation disorders sit outside of the WHO classification?
Hyperprolactinaemic amenorrhoea/anovulation (sits outside WHO classification)
Management of WHO Group I ovulation disorders (Hypothalamic pituitary failure e.g. Stress, anorexia, exercise induced)
Increase BMI if <19 kg/m2
Reduce exercise if high levels
Pulsatile GnRH or Gonadotrophins with LH activity to induce ovulation
Management of WHO Group II ovulation disorders
Hypothalamic-pituitary-ovarian dysfunction e.g PCOS
Weight reduction if BMI >30 Clomifene/ Clomiphene (1st line) Meformin (1st line) Combined clomiphene & Metformin (1st/2nd line) Laparoscopic drilling (2nd line) Gonadotrophins (2nd line)
Management of WHO Group III ovulation disorders
Ovarian failure
Management Group III
Consider IVF with donor eggs
Management of Hyperprolactinaemia related ovulation disorders?
Management of Hyperprolactinaemia induced ovulation disorder
Investigate cause e.g. MRI head (?pituitary adenoma) medication review (some antipsychotic medications can cause prolactin rise)
Dopamine agonist (Bromocriptine advised by NICE as 1st line)
What percentage of men with cystic fibrosis have subfertility?
98%
Typically due to failure of the vas deferens to develop properly
Normal semen volume
Semen volume: 1.5 ml +
Normal semen PH
pH: 7.2 +
Normal semen concentration per ml
Sperm concentration:
Greater than or equal to
15 million spermatozoa per ml
Normal total sperm count per ejaculate
Total sperm number: 39 million spermatozoa per ejaculate
Normal total sperm motility
total motility: 40% or more
progressive motility: 32% or more
Normal sperm vitality on semen analysis
Vitality: 58% or more live spermatozoa
Semen analysis % normal morphology
Sperm morphology (percentage of normal forms):
4% or more
Management of abnormal semen analysis
repeat sample in 3 months (unless severe azoospermia)
If abnormalities persist
then do hormone profiling (look for hypogonadotrophic hypogonadism which may be treatable with gonadotrophins)
What percentage of couples with subfertility have unexplained subfertility
30-40%
of subfertile couples have unexplained subfertility
Serious adrenal or ovarian pathology is suggested by a Female testosterone level greater than what
Testosterone levels greater than
5 nmol/L (or 1.5ng/ml)
point towards serious ovarian or adrenal pathology
Psychological effects of subfertility
Can affect both partners stress relationship impact reduce libido Financial concerns and pressures Uncertainty Anxiety Low mood Grief Anger Denial Loss of self esteem or self worth Guilt Feeling of a lack of control Altered sleep
Management of psychological consequences and contributors of sub-fertility
Inform re fertility support group
offer counselling
Relaxation techniques
Medication if diagnosed mental health condition and benefits outweigh risks to potential pregnancy
For people using artificial insemination to conceive what is the usual conception rate?
using artificial insemination to conceive for F <40
> 50% women conceive within 6 cycles IUI
A further half will conceive with a further 6 cycles
cumulative pregnancy rate ~ 75%
Advice re alcohol for couples trying to become pregnant
Women should drink no more than 1 - 2 units of alcohol once or twice per week and avoid episodes of intoxication
Men should should not exceed 1-2 units per day to avoid affecting semen quality / sperm count
Advice re smoking for couples trying to become pregnant
Women who smoke should be informed this is likely to reduce their fertility
offer referral to a smoking cessation programme
Passive smoking is likely to affect chance of conception
Men who smoke have a risk of reduced semen quality. Stopping smoking will improve general health.
Features of ovarian hyperstimulation syndrome
Abdo pain Ascites Hypovolaemic shock Pleural effusion Thrombosis Retail failure Death
What is maximum ovum survival believed to be?
24 hours
What is maximum sperm survival believed to be?
7 days
Where are spermatozoa produced and where do the become motile?
Produced in seminiferous tubules and become motile il the epididymis
Where is inhibin produced
Sertoli cells
What does a secondary spermatocyte divide into
2 spermatids
What does a primary spermatocyte divide into
2 secondary spermatocytes
What are primary spermatocytes formed from
Spermatogonium
Does smoking cigarettes affect female fertility?
Yes.
There is a direct correlation between the number smoked and the incidence of female infertility
Main causes of infertility in the UK
Factors causing male infertility (30%) Ovulatory disorders (25%) Tubal damage (20%) Uterine or peritoneal disorders (10%) No cause identified (25%)
Advice re caffeine for a couple trying for pregnancy
No consistent evidence of an association between caffeine and fertility problems
Advice re high BMI for a couple trying for pregnancy
- Women with a BMI of 30+ are likely to take longer to conceive
- Women with a BMI 30+ and not ovulating will increase chance of conception by losing weight.
- Participating in a group programme involving exercise + dietary advice leads to more pregnancies than weight loss advice alone.
- Men with a BMI 30+ are likely to have reduced fertility
Advice re low BMI for a couple trying for pregnancy
Women with a BMI <19 and have irregular menstruation / amenorrhoea - increasing body weight likely to improve chance of conception
Advice re tight underwear for a couple trying for pregnancy
Men - association between elevated scrotal temperature and reduced semen quality.
Uncertain if loose-fitting underwear improves fertility
When should a referral to fertility services be made before 12m of attempting conception?
Earlier referral for specialist consultation where:
- woman aged 36 years or over
- Known clinical cause of infertility or history of predisposing factors
- if treatment is planned that may result in infertility (such cancer tx)
investigatory steps for a couple with fertility difficulties
semen analysis Menstrual cycle regularity F FSH level and progesterone F prolactin level - if ovulation disorder or galactorhoea STI screen Hysterosalpingography if no risk factors for tubal disease, otherwise lap and dye Rubella susceptibility test recent cervical smear HIV, Hep B and C if having IVF
Is screening for anti-sperm antibodies recommended for investigating subfertility?
No, no evidence of effective treatment
management if initial semen test is abnormal
repeat semen test 3m later
Allows for complete spermatozoa cycle to be completed
Offer repeat earlier if severe oligozoospermia / azoospermia
What is the first line measure of female ovarian reserve?
age
Are ovarian volume and ovarian blood flow markers of fertility
No
Not reccommended
Are onhibin B and
oestradiol (E2) levels recommended for subfertility investigation
No
Timing of a progesterone blood test for fertility investigation?
Mid-luteal phase
Day 21 of a 28‑day cycle
To confirm ovulation
Timing of a progesterone blood test for fertility investigation if F has irregular / absent cycle
random
or calculate from timing of prev cycles and repeat weekly until next cycle starts
For a sero-discordant HIV couple with a +ve M, the transmission is low from UPSI if what 4 conditions are met
- Compliant with ARVs
- Plasma VL undetectable for 6m+
- no other infections present
- UPSI limited to time of ovulation
when should sperm washing be offered
If serodiscordant couple where +ve male partner is non compliant with ARVs or VL is not <50 or has notbeen <50 for >6m
What effect does sperm washing have on the risk of HIV transmission to the F
Reduces it
but does not eliminate the risk
why are women offered rubella susceptibilty testing at fertility clinics
to enable offer of vaccination if susceptible
Why is an STI test recommended for investigation of fertility patients
to exclude infection before undertaking uterine instrumatation / HSG which could promote PID / spread
Management of men with leucocytes in semen analysis
None
Treat with antibiotics only if symptoms of infection
Management of known antisperm antibodies
Explain the significance of antisperm antibodies is unclear
The effectiveness of systemic corticosteroids is uncertain
Management of men with obstructive azoospermia
Offer surgical correction of epididymal blockage - likely to restore patency and improve fertility.
Or surgical sperm recovery and IVF
Management of varicoceles in a couple with subfertility
Men do not offer surgery for varicoceles for fertility treatment
- does not improve pregnancy rates.
Monitoring ovulation induction during gonadotrophin therapy for fertility patients
ovulation induction with gonadotrophins = risk of multiple pregnancy and ovarian hyperstimulation
Ovarian ultrasound monitoring - measure follicular size and number
risks of ovulation induction with gonadotrophins
risk of multiple pregnancy and ovarian hyperstimulation
Management of fertility patient with mild tubal disease
tubal surgery may be more effective than no treatment.
Or tubal catheterisation / hysteroscopic cannulation
Management of fertility patient with hydrosalpinges
offer salpingectomy
preferably laparoscopically
before IVF
improves chance of live birth
Management of fertility patient with intrauterine adhesions
hysteroscopic adhesiolysis
management of unexplained infertility
DO NOT offer ovarian stimulation agents
Regular UPSI for 2 years
then consider IVF
when is intrauterine insemination considered as a treatment option for fertility
People who are unable to, or find it very difficult to, have vaginal intercourse because of a clinically diagnosed physical disability or psychosexual problem
Conditions requiring specific consideration in relation to method of conception (e.g. after sperm washing)
Same sex relationships.
management of people recommended to try IUD and who do not conceive after 6 cycles of insemination.
Confirm evidence of normal ovulation, tubal patency and semenalysis.
Offer further 6 cycles of unstimulated IUI before IVF considered
factors predicting IVF success
Female age Number of previous treatment cycles previous pregnancy history BMI alcohol intake smoking caffeine consumption
How does previous pregnancy history influence IVF outcome
IVF treatment is more effective in women who have previously been pregnant and/or had a live birth
Recommended BMI for IVF treatment to increase chance of success
Aim for 19-30.
Ideally 19-25 is preferable.
BMI >30 will reduce success rates
what is the NICE recommended IVF treatment for women under 40
<40yo
Not conceived after 2 yr regular UPSI or 12 cycles of IUI
offer 3 full cycles of IVF
With or without ICSI
If F reaches age 40 during treatment complete current full cycle but do not offer further full cycles
what is the NICE recommended IVF treatment for women age 40-42
F aged 40–42
Not conceived after 2 years regular UPSI or 12 cycles IUI
offer 1 full cycle of IVF
With or without ICSI,
provided 3 criteria are met:
- never previously had IVF
- No evidence of low ovarian reserve
- Discussion of additional implications of IVF / pregnancy at this age
Pre-treatment for IVF
Pre-treatment with oral contraceptive pill or progestogen) as part of IVF does not affect the chances of having a live birth.
Consider pre-treatment in order to schedule IVF treatment for women who are not undergoing long down-regulation protocols
Down regulation protocols in IVF
Down regulation / other regimens used to avoid premature LH surges in IVF
Use GnRH agonist down-regulation or GnRH antagonists
Only offer GnRH -agonists to F with low risk of OHSS
When using GnRH -agonists use a long down regulation protocol
How is controlled ovarian stimulation in IVF achieved
Ovarian stimulation as part of IVF
Use urinary or recombinant gonadotrophins.
Individualised starting dose of FSH Based on factors that predict success - age - BMI - presence of polycystic ovaries - ovarian reserve DO NOT use >450 IU/day of FSH
How is ovulation triggered in IVF
Offer women human chorionic gonadotrophin to trigger ovulation in IVF treatment.
+ ultrasound monitoring of ovarian response
Management of a patient undergoing oocyte retrieval in IVF
TV retrieval of oocytes - offer conscious sedation
When should follicle flushing be offered when retrieving oocytes for IVF
If less than 3 follicles have developed
Management of embryo transfer stages in IVF
- Ultrasound-guided embryo transfer improves pregnancy rates.
- Only place embryos into a uterine cavity with an endometrium of 5 mm +
- Bed rest of more than 20 minutes’ duration following embryo transfer does not improve the outcome of IVF treatment
- Evaluate embryo quality, at both cleavage and blastocyst stages
NICE recommendations for number of embroyos to be transfered during IVF aged <37yo
For women <37 yrs:
- 1st full cycle - transfer 1 embryo
- 2nd full cycle use 1 top quality embryo or 2 lower quality embyos
- in 3rd cycle offer 2 embryo transfer
NICE recommendations for number of embryos to be transferred during IVF aged 37-39yo
For women 37-39 yrs:
- 1st and 2nd cycles - transfer 1 top quality embryo or 2 lower quality
- 3rd cycle offer 2 embryo transfer
NICE recommendations for number of embryos to be transferred during IVF aged 40+
For women 40yrs +:
- Consider 2 embryo transfer for all cycles
NICE recommendations for number of embryos to be transferred during IVF using donor eggs
Transfer strategy is based on the age of the donor
Luteal phase support after IVF
Offer progesterone for luteal phase support after IVF treatment.
Do not routinely offer HcG for luteal phase support = increased likelihood of OHSS
Evidence does not support continuing any form of treatment for luteal phase support beyond 8 weeks’
NICE guidance on Gamete intrafallopian transfer and zygote intrafallopian transfer
Insufficient evidence to recommend the use of gamete intrafallopian transfer or zygote intrafallopian transfer in preference to IVF
Indications for intracytoplasmic sperm injection
- severe deficits in semen quality
- obstructive azoospermia
- non-obstructive azoospermia.
And considered for couples where previous IVF resulted in failed / v. poor fertilisation
Advice for patients re Intracytoplasmic sperm injection versus IVF
ICSI improves fertilisation rates compared to IVF alone
But once fertilisation is achieved the pregnancy rate is no better than with IVF
Indications for donor insemination for fertility treatment
Effective in managing fertility problems associated with:
- obstructive azoospermia
- non-obstructive azoospermia
- severe deficits in semen quality in couples who do not wish to undergo ICSI
Consider if:
- high risk of transmitting a genetic disorder
- high risk of transmitting infectious disease
- severe rhesus isoimmunisation.
Indications for oocyte donation
Effective in managing fertility problems associated with:
- premature ovarian failure
- gonadal dysgenesis including Turner syndrome
- bilateral oophorectomy
- ovarian failure following chemotherapy or radiotherapy
- certain cases of IVF treatment failure
Considered in certain cases of high risk of transmitting a genetic disorder
What is the most common cause of spontaneous miscarriage and implantation failure in those undergoing IVF?
Aneuploidies
Azoospermia and normal FSH is consistent with what diagnoses? (3)
Obstructive cause
- congenital absence of the vas
- varicocele
- tubal blockage secondary to infection, trauma, surgery
Azoospermia and raised FSH is consistent with what diagnosis
Testicular failure
What signs of symptoms would merit admission for OHSS?
6
Tachypnoea / SOB Hypotension Tense ascites Oliguria Electrolyte imbalance Intractable vomiting
Classification of OHSS (1-5)
Mild = grade 1-2 1 = abdo distension and discomfort 2 = 1 + N+V, +/- diarrhoea + ovarian enlargement 5-12cm
Moderate = grade 3 = 2 + uss evidence of ascites
Severe = grade 4-5 4 = 3 + clinical ascites +/- hydrothorax +/- breathing difficulty 5 = 4+ increased blood viscosity, hypovolaemia, increased coagulation, decreased renal perfusion
Long term risks of premature ovarian insufficiency
Infertility CVD Reduced BMD Increased risk of osteoporosis Increased risk of Alzheimer's Decreased cognitive function Decreased verbal fluency Impaired memory
Diagnosis of POI
Age <40
Persistently elevated FSH >30 on 2 tests min 4 weeks apart
Altered menstrual cycle
Menopausal symptoms
What autoimmune causes of POI may occur (7)
Addisons Pernicious anaemia Hashimotos Idiopathic thrombocytopenic purpura Rheumatoid arthritis with vitiligo Cushings Myasthenia gravis
Timing for a mid-luteal progesterone sample
Day 21
Indication for a mid-luteal progesterone sample
Irregular menstrual cycle
Or fertility issues to confirm ovulation
What level for a mid-luteal progesterone sample is normal for an ovulating woman?
> 30 confirms ovulation
Effects of metformin used in treatment of PCOS
Decrease insulin secretion (not effective for weight loss) Increased conception rate Improved insulin sensitivity Deceased androgen levels Decreased hepatic gluconeogenesis
Roe of FSH in men
Stimulates formation of sperm in the testes
How many days does the process of spermatogenesis take?
70 - 80 days
Impact of sulfasalazine on semen analysis
Decrease sperm count
Decrease sperm motility
Increase abnormal forms
Reversible after drug cessation
