2: Fertility and Sub-Fertility: Causes, IVF Flashcards
Define sub fertility
Failure to conceive despite one-year of unprotected sex, in absence of known cause infertility.
What is infertility
No possibility of conceiving
What is primary sub-fertility
When women has not conceived previously
What is secondary sub-fertility
Women has conceived previously
What % of couples can conceive in one-year
80
What is mnemonic to remember causes of infertility
UMATE
What are the causes of infertility
Unexplained (28%) Male (25%) Anovulation (21%) Tubal (20%) Endometriosis (8%)
In males, how can causes of infertility be divided
- Sperm
- Azoospermia
- Inflammation
- Coitus
What is the most-common cause of infertility in males
Semen abnormality
What proportion of infertility is due to semen abnormality
85%
What is oligospermia
Decrease number of sperm in ejaculate
What are 4 causes of oligospermia
- Testicular cancer
- Varicocele
- Alcohol
- Idiopathic
- Rec drugs
What proportion of male infertility is due to azoospermia
5%
Define azoospermia
Complete absence of sperm in ejaculate
How can causes of azoospermia be classified
Pre-testicular, Obstructive, Non-Obstructive
What are 3 pre-testicular causes of azoospermia
- Hypogonadotorphic hypogonadism
- Kallman’s
- Anabolic steroids
What are 4 causes of obstructive azoospermia
- Congenital absence vas deferens (CF)
- Vasectomy
- Gonorrhoea
- Chlamydia
What can cause a congenital absence of the vas deferens
Cystic fibrosis
What are 3 non-obstructive causes of azoospermia
Klinfelter’s (XXY)
Chemotherapy
Cryptochidism
Orchitis
What are 3 inflammatory causes of male infertility
- Antibodies = reversal vasectomy
- Infective
- idiopathic
What are coitus causes of male infertility
Erectile dysfunction
What two medications can cause erectile dysfunction
B-blockers
SSRIs
What are the 3 cause of female infertility
- Anovulation
- Tubal
- Endometriosis
What are two types of anovulation
Primary and Secondary
What is primary anovulation
Anovulation due to pathology in the ovary
What are 4 causes or primary anovulation
- PCOS
- Tuners (45XO)
- Premature ovarian failure
- Iatrogenic: chemoradiotherapy
what is secondary anovulation
Anovulation due to problems with pituitary or hypothalamus
what are 5 causes of secondary anovulation
Kalmann’s
PCOS
Anorexia
Hyperprolactinaemia
What are 2 -tubal causes of female infertility
- PID
2. Previous surgery
Explain endometriosis as cause of infertility
Endometriosis causes inflammation, which can lead to scarring which can cause tubal occlusion.
In male ‘work-up’ for infertility what two things need to be established in history
- Alcohol and Smoking = both can cause subferility
- Medications = some can lead to ED
On examination, what 3 aspects may be focused on
- Secondary sexual characteristics (absence of)
- BMI
- Testicular volume
What can obesity cause
Subfertility
What can absence of secondary sexual characteristics be caused by
Klinfelter’s
After history and examination, what should be tested in male infertility
Semen analysis
In semen analysis what do WHO define as normal progressive motility
32%
In semen analysis what do WHO define as normal total motility
40%
In semen analysis what do WHO define as normal morphology
> 4%
Why may FSH be tested for male infertility
Will be raised in testicular failure
Why may LH be tested in male infertility
Low in androgen deficiency
What karyotyping may be ordered for male infertility
- Klinefelters (XXY)
- Cystic fibrosis - congenital absence VD
In history for female infertility what should be focused on
Alcohol and Smoking - Decrease fertility
Previous STI or pelvic surgery - tubal occlusion
What should be looked for on examination in female infertility
BMI Hirsuitism - PCOS Absence secondary characteristics Visual field defect - prolactinoma Pelvic mass
What test is ordered to determine ovarian reserve
FSH
When should FSH be measured
Day 2-4 of cycle
What is normal for FSH
> 10
What is used to determine if individual is ovulating
Mid-luteal progesterone
When should progesterone be performed
7d prior to first-day menses
In a 28-day cycle, when should mid-luteal progesterone be performed
day 21
What level of mid-luteal progesterone indicates a women is ovulating
> 30
if a women has a mid-luteal progesterone of 16-30 what is done
Repeat test
If a women has a mid-luteal progesterone of less than 16 what is done
Refer
What is done for following mid-luteal progesterones
a. > 30
b. 16-30
c. <16
a. Nothing = normal
b. repeat test
c. refer
What is gold-standard test to examine tubal latency
Laparoscopy and methylene blue dye
Explain laparoscopy and dye
Dye is injected into cervix and laparoscopy used to examine tubal patency
What is hysteroscopesalpingogram
Contrast dye injected. X-rays used to visualise
What is hysteria-salpingo contrast sonography (HyCoSy)
Contrast injected, Trans-vaginal US used to examine tube patency
What are 4 lifestyle factors in males that can improve fertility
- Smoking cessation
- Reduce alcohol
- Medication review (If ED)
- Weight loss if BMI over-30
What is second-line for male infertility
Multivitamin
What does the multi-vitamin given for male subfertiltiy contain
Zinc
Selenium
Vitamin C
What is follow up after giving tablet containing zinc, selenium and vitamin C
3-months to check semen
What is third-line for managing infertility
Intracytoplasmic sperm insemination (ICSI)
What are 4 female lifestyle factors used to treat sub fertility
- Smoking cessation
- Weight loss
- Folic acid
- Regular sexual intercourse
How often should a couple trying to conceive have sex
2-days
What causes 80% of anovulation in females
PCOS
What is first-line for managing PCOS
Weight Loss
What is second-line to manage sub-fertility in PCOS
Clomiphene citrate
Explain how clomiphene is given
Day 2-6 of the cycle
How does clomiphene work
It is anti-oestrogen, so works to increase FSH
What is required in PCOS after giving clomiphene
US - to check for ovarian hyper stimulation
What is third-line for managing sub-fertility in PCOS
Laparoscopic ovarian drilling
What is laparoscopic ovarian drilling
Diathermy used to drill holes in ovary
What is used for clomiphene-resistant PCOS
Gonadotrophins
What are two indications for donor insemination
- Same-sex couple (Female)
- Male has azoospermia, with abnormal semen analysis and failure of ICSI
What is intracytoplasmic sperm injection
Sperm is taken from ejaculate or surgically from testes. Then injected into ova
When is intracytoplasmic sperm injection (ICSI) used
IVF Failed
Abnormal sperm parameters
What is intrauterine insemination
Sperm is taken form ejaculate. Or, surgically from testes and injected into uterus.
What may intrauterine insemination be combined with
ovarian stimulation
What are indications for intrauterine insemination (IUI)
- Mild azoospermia
What is in-vitro maturation
Immature eggs taken from ovaries and ICSI
What is ooplasmic transfer (OT) or nuclear transfer (NT)
Baby has two mothers one donates ova and other cytoplasm.
What does ooplasmic transfer count as
Human genetic modification
What are 5 indications for IVF
- Tubal occlusion
- Maternal age impact fertility
- Unexplained sub-fertility for 2-years
- Endometriosis
- Infertility not responding to clomiphene
What should couples before IVF be screened for
HIV
Hep B
Hep C
What are the 5 steps of IVF
- Ovarian Stimulation
- Oocyte retrieval
- Fertilisation
- Embryo transfer
- Luteal support
What is the first-stage of IVF
Ovarian stimulation
What is given in ovarian stimulation.
GnRH analogue or agonist
What is the role of GnRH agonist
Down-regulates women HPA axis
when is GnRH agonist given
Day 21 (mid-luteal) until day 10
what is then given
FSH
what is the role of FSH
Stimulate follicle development
what is given after FSH and why
hCG - matures follicles
what is the second-stage of IVF
Oocyte retrieval
how long after hCG given are oocytes retrieved
36-hours
what is used to retrieve follicles
trans-vaginal needle aspiration
what is stage 3 of IVF
fertilisation
what is culture of sperm and oocyte referred to as
‘day 0’
what days are embryos transferred into women uterus
2-3 or day 5 (blastocyst)
what is the embryo at day-5
Blastocyst
what is the maximum number of embryos transferred
2
what is stage-5 of IVF
Luteal support
what is given in stage-5
Progesterone
What factors improve success of IVF
Younger Age
Previous pregnancy
Shorter duration sub-fertility
What factors reduce success of IVF
Obese
Smoking
Low AMH
What is role of COCP in IVF
Given 1-2W prior to stimulation to suppress cycle
What is the role of gonadotrophin analogue in IVF
Suppresses cycles
What is role of FSH in IVF
Increases follicle development
What is role of bHCG
Acts a luteinising hormone surge - causing oocyte to separate from follicle
What are both men and women given in IVF and why
Doxycycline - prevents infection that may impact implantation
When should men take doxycycline
7d prior to retrieval
When should women take doxycycline
4d prior to retrieval
What is ovarian hyperstimulation syndrome
Complication of stimulation in fertilisation treatment
What are 4 RF for ovarian hyperstimulation syndrome
- Young
- Low BMI
- Previous OHSS
- PCOS
When do individuals with OHSS present with symptoms
5-7 after-induction
Or, 12-15d after pregnancy
What are mild symptoms of OHSS
Abdominal pain
Abdominal bloating
What are moderate symptoms of OHSS
Abdominal pain
Abdominal bloating
N+V
US evidence ascites
What are severe symptoms of OHSS
Abdominal pain Abdominal bloating N+V Clinical evidence ascites Oliguria High haematocrit Hypoproteinaemia
What are severe symptoms of oHSS
Abdominal pain Abdominal bloating N+V Clinical evidence ascites Anuria ARDS VTE
Explain pathophysiology of OHSS
When stimulated there can be multiple lutenised corpus luteum cysts which release oestrogen, progesterone and VEGF. VEGF causes increases in membrane permeability - accumulation fluid in pleural and peritoneal space.
What are two features of OHSS
Ovarian enlargement
Fluid shift - pleural or peritoneal spaces
What is criteria for offering IVF in women under-40
Offer 3-cycles of IVF if: 2-years unprotected intercourse trying to conceive with 12 cycles of artificial insemination (or 6 IUI)
What is criteria for offering IVF in women 40-42
Offer 1-cycle if: 2-years unprotected intercourse or 12-cycles artificial insemination (6 IUI) and
- No previous IVF
- No evidence low ovarian reserve
- Understands risk of pregnancy in this age
What is the NHS criteria for funding IVF
- No children
- BMI <30
- Non-smoker
- <42
What act regulates IVF
Human Fertilisation and embryology act
Explain HFEA criteria for gamete donors
- No medical or psychiatric conditions
- Known or anonymous
- Can only be used in up-to 10 families
- Full infection screen
- <35
- Counselled
Can children know about their donors
Once 18, children can contact HFEA to find-out information about their donors