Infertility Flashcards
Define and briefly describe the problem of infertility
- 85% of couples will conceive in 1 year if having regular intercourse
- the rest are infertile or subfertile
- Infertility = inability to conceive after one year of unprotected intercourse
- 1/6 couples will have fertility issues at some stage in their lives
- 30%/30%/30% = female/male/combined
- 10% unexplained
List causes of male infertility
Five main reasons for male infertility:
- sperm count either azoospermia or oligospermia – normal count is greater than 15 million
- sperm quality: motility (asthenospermia) – must have minimum greater than 50% motile – or morphology (teratospermia) – must have over 4% with normal morphology
- anti sperm antibody
- sexual dysfunction e.g. erection and ejaculation
- lifestyle factors —> obesity can cause oligospermia or azoospermia due to oestradiol production from excess adipose
List causes of azoospermia
- Absent sperm production
– Testicular: Primary testicular failure (seminiferous tubules failure)
Congenital: Klinefelter’s 47XXY, cryptorchidism ^[undescended testes], microdeletion Y chromosome ^[loss of Daz gene], Sertoli cell only syndrome.
Acquired: mumps orchitis, torsion, castration
Iatrogenic: radiotherapy, chemotherapy
– Pretesticular: Secondary testicular failure
Hypothalamic: Kallman’s syndrome, idiopathic hypogonadotrophic hypogonadism, hemochromatosis
Pituitary: trauma, meningitis, tumours ^[e.g. acromegaly], isolated FSH deficiency
Acquired: Anabolic steroids, testosterone injection - Obstruction of genital tract
– Congenital: CBAVD cystic fibrosis
– Acquired: STDs, TB, chlamydia ^[and associated scarring]
– Iatrogenic: vasectomy, hernia/hydrocele repair ^[scarring]
What action can be taken regarding male infertility?
- Lifestyle change
- weight loss and exercise
- Reduce alcohol, stop smoking!
- Alter medications: beta blockers and ED, anti-depressants and libido
- Better management of medical conditions: T1D in males can cause retrograde ejaculation due to neuropathies
- Oxidative stress and excessive reactive oxygen species is
thought to cause sperm DNA damage.- Increased turnover of sperm may reduce sperm chromatin damage
- Increase intake of more antioxidant
- Consider pharmacological treatment of erectile dysfunction
List causes of female infertility
Five causes of female infertility:
- ovulatory disorders e.g. PCOS, associated with weight; hypothalamic e.g. elite athletes, underweight, eating disorders
- anatomical problems e.g. fallopian tube occlusion, fibroids, septum
- endometriosis ^[causes severe pain, but does not always present as such in all women]
- sexual dysfunction: dyspareunia
- lifestyle factors e.g. poor sleep and cycling issues
Define and describe fecundability
- monthly chance of pregnancy
- In a normal couple in their 20s = 20%
- a reduction with aging is well documented
- 33% of women delaying pregnancy to late 30s have fertility problems
- 50% delaying pregnancy to after 40 have fertility problems
Describe the effect of aging and fertility
studies
- French Donor Insemination study
– <age 31, 74% conceive in 1 year
– Ages 31 –35, 62% conceive in a year - Dutch DI study
– The chance of having a healthy baby decreases by 3.5% per year after age 30.
– A woman age 35 has 50% the chance of having a baby as a 25 year old
Describe statistics regarding likelihood of fertility and factors that contribute to increased time to pregnancy
- Monthly fertility for a normal young couple is 20%
- After 3 years infertility the monthly fertility rate is 4.6% if there are no known abnormalities
- Multiple minor abnormalities have an additive effect on infertility
- Generally refer to specialist after 12 months of trying in women < 35, 6 months of trying if > 35.
- Refer early if patient known to have multiple fertility issues
List and describe the effect of multiple minor abnormalities of fertility
- reduces fecundability
- chance of falling pregnant in 2 or 3 years
- lengthens time to pregnancy
- important for stratification for referral
- also highlights need to investigate all subfertile factors, in both partners
Why does aging impact fertility?
- mitochondrial dysfunction
- increased prevalence of aneuploidy in aging oocytes
- spindle cell dysfunction leading to formation of aneuploid embryos
- increased incidence of spontaneous miscarriage
Miscarriage can be considered a product of aneuploidy and mitochondrial dysfunction. Risk increases with age.
Simply, with age:
- decreased egg quality
- decreased egg quantity
- increased aneuploidy risk
- increased miscarriage risk
Note: average risk regardless of age is 15%.
Becomes 25% in 35-39, 50% in 40-44 range, and 90% over 45 years.
HI
List investigations of an infertile couple
- try and treat couple and see them together
- take full medical history from both
- family history may be relevant - genetic conditions
- consider potential impact of medicaitons on male and female fertility
- consider weight and lifestyle factors
Describe features of a good gynaecological history
- Menstrual cycle - how many days
- Symptoms of PCOS - oily skin, hirsutism, weight gain
- Symptoms of endometriosis - pain in periods, between periods, sex, bowel movements
- Past history of STIs
- Past obstetrics history
- Past gynaecological surgery
- Past fertility treatment
What are some investigations that can be done in the female?
- Cervical screening
- Antenatal screen
- Hormone day 2: LH, FSH, prolactin, TFT, FAI ^[PCOS raised], SHBG ^[down in PCOS], testosterone ^[free fraction increases] for baseline ovarian reserve and assessment of PCOS (also rubella?)
- Day 21: estrogen, progesterone to confirm ovulation
- Antimullerian hormone
- Pelvic ultrasound for anatomical survey, tubal patency (Hycosy), antral follicle count and signs of endometriosis
- Or Hysterosalpingogram ( Xray ) for tubal patency
What are some investigations that can be done in the male?
- Semen analysis: “SFA + IBT”
= Volume, concentration, motility, morphology and antisperm antibody screen - Do not rush in to repeat semen analysis if initial abnormal, wait 12 weeks to repeat (Refer to a dedicated andrology laboratory)
- FSH, LH, testosterone, thyroid function and prolactin if oligospermia
very low
Discuss the AMH test
– Can perform anywhere in menstrual cycle
– OCP or any hormonal contraception may reduce level
– Some intra-individual variation : best to repeat if big decisions are about to be made on it
* Shall I order it?
– Will it change behaviour or management
– Careful counseling especially in single women
– What would you do if it’s normal
– What would you do if it’s abnormal
List some basic fertility advice
- Lifestyle changes
- Lose weight, exercise!
- Diary of menstrual history
- Temperature chart, ovulation detection kit
- Optimise management of medical condition
List indications for IVF
- Tubal obstruction
- Endometriosis
- Unexplained infertility
- Male factor infertility
- Pre implantation genetic diagnosis (no fertility issues, seeing if child will have genetic issues)
List the IVF process
- stimulate the ovaries
- egg and sperm collection
- fertilising and nurturing embryos in lab
- transferring embryo
- luteal phase support (progesterone) and pregnancy test
Describe the issue fo controlled ovarian hyperstimulation
- Each month a woman will develop between 1 and 30
follicles in her ovary in each menstrual cycle - In IVF, FSH is injected to encourage more follicles to
develop into mature eggs. - Challenges in IVF :
- Prevention of surge of LH leading to ovulation, hence the need for pituitary desensitization with use of GnRH analogue
- Prevention of ovarian hyperstimulation syndrome
- Contemporary management of IVF look at ways to reduce OHSS as well as reducing side effects from prolong GnRH suppression.
Describe ICSI and indications
- A single sperm is injected into an oocyte
- Once successfully fertilised the embryo is left to develop in our lab over the next 5 to 6 days
- Once developed, the embryo is transferred to the
uterus
#### Indications - Treatment for male factor infertility
– Obstruction
– Oligospermia
– Poor motility
– Poor morphology
– Sexual/erectile problems eg.Spinal cord injuries
– Genetic disorders/PGD eg. Cystic fibrosis
List practicalities and limitations of PGD
- Molecular diagnosis to be known in advance i.e. need to know gene/s that may be mutated
- May involve local/overseas diagnostic or research lab. Best to have been worked up by ACT Genetics.
- Referral to fertility specialist to commence PGD workup. (Patient will need to see geneticist and PGD scientist)
- PGD by either direct PCR or indirect testing of linkage study or both.
- PGD workup and embryo biopsy for PGD now covered by Medicare
Limitation of PGD
* Clinical problems with ART: challenges with IVF stimulation in older patients
* Analysis successful in 90% of embryos
* Mosaicism: dilemma in managing embryos with
mosaic results, occurs in 20% of embryos
* Technical problem: inconclusive result/test fail
* No embryos to transfer: no normal embryos suitable
* No pregnancy: 50-60% chance of pregnancy but not
100%.
* Cost
List some indications for fertility preservation
- Medical or social indication
- Effect of chemotherapy on ovarian reserve- depletion
of primordial follicle pool - Alkylating agents ie Cyclophosphamide in breast
cancer treatment - Patients should be offered oncofertility counselling
- Oocyte or embryo vitrification, ovarian tissue cryo-
preservation or GnRHa suppression
