fertility Flashcards
OHSS
Ovarian hyperstimulation results after the exposure of the ovaries to the hormones from the IVF cycle and results in a proinflammatory condition leading to increased vascular permeability and hypovolemia.
OHSS is a self limiting condition
This risks are dehydration, pain, renal failure, respiratory distress torsion and VTE
The investigations we need to perform include daily weights and girth, FBC haematocrit, U+E, Cr, osmolality, LFTs, CRP, coags, hcg, pelvic USS
Management is conservative.
Input output monitoring, fluid replacement and use of albumin if needed, pain relief - avoid NSAIDS, thromboembolism prophylaxis
inform fertility team
Paracentesis is indicated if severe pain, respiratory distress or oliguric from increased abdominal pressures.
Surgery if bleeding or torsion
how to assess the infertile man
History
• Developmental history
• Testicular descent, pubertal development, loss of body hair, or decrease in shaving frequency
• Medical history including
• Chronic medical illness and infections, such as mumps orchitis, sinopulmonarysymptoms, sexually transmitted or genitourinary tract infections including prostatitis
• Procedures involving the inguinal and scrotal areas such as vasectomy, orchiectomy and inguinal hernia repair
• Drug and environmental exposures – alcohol, smoking, steroids, chemotherapy, drugs that raise prolactin, exposure to toxic chemicals, radiation, recreational drugs
• Sexual history: libido, frequency of intercourse, and previous fertility assessment
• School performance: history of learning disabilities suggestive of Klinefelter’ssyndrome
Examination
• general observation
• general appearance, including height, weight, blood pressure and pulse
eunuchoid - suggest androgen deficiency prepuberty
• increased body fat and decreased muscle mass suggest androgen deficiency
• gynecomastia - decreased androgen to oestrogen ratio
general medical examination
• manifestations of androgen deficiency depend upon the age of onset
skin and appendages
• long-standing androgen deficiency
• loss of pubic, axillary and facial hair
• decreased oiliness of the skin
• fine facial wrinkling
Examination
External genitalia
• Tanner stage 5 of phallus and testes
• examination of the scrotum for absence of the vas, epididymal thickening, varicocele, and hernia
• a varicoceleis confirmed with the man standing and performing a Valsalva maneuver
• Praderorchidometeror calipers
reflects decreased volume of the seminiferous tubules
• normal volume > 15 ml
ddx
pretesticular
genetic
Idiopathic Hypo hypo - GnRH deficiency
Kallmans is GnRH deficiency with anosmia (can have without anosmia too)
Can be idiopathic or X linked recessive disorder (also linked to colour blindness, facial defects and renal abnormalities)
Haemochromotosis
Prader Willi
Laurence –mood Biedl syndrome
Pituitary and hypothalmic tumors
Congenital combined pituitary hormone deficiency
acquired
Pituitary tumors, sellar masses, prolactinomas, surgical or RT
Infiltrative disease eg sarcoid, TB, fungal, iron overload
Lymphocytic hypophysitis - autoimmune
Trauma
Vascular lesions eg infarct
Endocrine - Hyperprolactinoma, estrogen excess (secondary from topical or testicular tumor) glucocorticoid excess (Cushings) androgen excess tumors) thyroid disease (high or low) CAH
Drugs/ hormone states that increase prolactin, tesosterone or estrogen
obesity
chronic nutrient deficiency
Testicualr
Idiopathic
Genetic / congenital
Y chromosome microdeletions / Autosomal and X linked defects
Klinefelters - (imp spermatogenesis and testosterone deficiency) 1:500 males XXY
(highest risk is non obstructive azoospermia – assess FHx malformation, recurrent abortions, low IQ)
Cryptorchidism (undescended testes) 2-5% newborns, higher in preterm. Increased risk impaired spermatogenesis and tumors
Myotonic dystrophy
Androgen receptor or biosynthesis disorder partial or mild androgen insensitivity / 5a reductase deficiency
acquired
Varcicocele - dilation of the pampiniform plexus of the spermatic veins in the scrotum L>R
NICE – surgery does not improve pregnancy rates
Cochrane review says it helps semen analysis
Trauma
Infection - Viral orchitis especially mumps, TB, leprosy, STIs,
Drugs - alkylating drugs eg cyclophosphamide (chemo) Cimetidine (H2 antagonist that interferes with spermatogenesis but competing with the androgen receptors thus affecting sertoli cell function) Hydroxyurea causes testicular failure.
Antiandrogens can affect sperm production as does ionising radiation - flutamide and cyproterone, spironolactone, ketoconazole
Environmntal factors - Pesticide, lead, cadmium and mercury, some insecticides and fungacides
Radiation
Smoking drops sperm count
Hyperthermia
Systemic disorders – sickle cell – cause cause testicular infarcts (also hypo hypo from iron overload)
CKD / cirrhosis / malnutrition
Anti sperm antibodies – impair motility, and cervical mucus penetration interfere with the acrosomal reaction, and sperm binding to the zona pellucida
post testicular
Epididymis
Absence – CBAVD 82% of the time its CF gene
Infection / drugs or toxins can cause dysfunction
sexual dysfunction
vasectomy
Investigations • semen analysis 2-7 days after sexual abstinence Repeat testing should occur 3 months after the initial analysis to allow for the cycle of spermatozoa to be completed If gross deficiency – repeat ASAP Other investigations performed on the basis of clinical presentation • karyotype • Y chromosome microdeletion • CFTR • LH, FSH, total testosterone • TSH, T4, prolactin • FBE, ELFT, iron studies
Initial management
all males should receive the following advice:
- where applicable, cease recreational substance abuse, including alcohol and nicotine
- where applicable, reduce body weight to normal recommendations
- where applicable, optimal control of pre-existing medical conditions
- exercise in line with NHMRC recommendations
- commence a multivitamin preparation with appropriate antioxidants, such as vitamin C or E, as these have been associated with an increased chance of conception in assisted reproduction
- management of specific conditions is dependent on the clinical presentation
how to assess the infertile man
History
• Developmental history
• Testicular descent, pubertal development, loss of body hair, or decrease in shaving frequency
• Medical history including Chronic medical illness and infections, such as mumps orchitis, sinopulmonarysymptoms,
sexually transmitted or genitourinary tract infections including prostatitis
• Procedures involving the inguinal and scrotal areas such as vasectomy, orchiectomy and inguinal hernia repair
• Drug and environmental exposures – alcohol, smoking, steroids, chemotherapy, drugs that raise prolactin, exposure to toxic chemicals, radiation, recreational drugs
• Sexual history: libido, frequency of intercourse, and previous fertility assessment
• School performance: history of learning disabilities suggestive of Klinefelter’s syndrome
Previous fertility hx - prev pregnancies
Examination
• general observation statue H W BMI eneral obs
• general appearance, including height, weight, blood pressure and pulse
Androgen deficiency:
• increased body fat and decreased muscle mass
• gynecomastia
STCR B
Tanner stage - pubic and axillary hair
External genitalia
• examination of the scrotum for absence of the vas, epididymal thickening, varicocele, and hernia
• Praderorchidometeror calipers
reflects decreased volume of the seminiferous tubules
• normal volume > 15 ml
ddx
pretesticular
Idiopathic
genetic
GnRH deficiency (Kallmans is GnRH deficiency with anosmia
X linked recessive disorder
Haemochromotosis
Prader Willi
Pituitary and hypothalmic tumors
Congenital combined pituitary hormone deficiency
acquired / masses / prev surgery or RT
Infiltrative disease eg sarcoid, TB, fungal, iron overload
Lymphocytic hypophysitis - autoimmune
Trauma
Vascular lesions eg infarct
Endocrine - Hyperprolactinoma, estrogen excess (secondary from topical or testicular tumor) glucocorticoid excess (Cushings) androgen excess tumors) thyroid disease (high or low) CAH
Drugs/ hormone states that increase prolactin, tesosterone or estrogen
obesity
chronic nutrient deficiency
Testicualr
Idiopathic
Genetic / congenital
Y chromosome microdeletions / Autosomal and X linked defects
Klinefelters - (imp spermatogenesis and testosterone deficiency) 1:500 males XXY
Cryptorchidism (undescended testes) 2-5% newborns, higher in preterm. Increased risk impaired spermatogenesis and tumors
Myotonic dystrophy
Androgen receptor or biosynthesis disorder partial or mild androgen insensitivity / 5a reductase deficiency
acquired
Varcicocele
Trauma
Infection - Viral orchitis especially mumps, TB, leprosy, STIs,
Drugs - alkylating drugs eg cyclophosphamide (chemo) Cimetidine / Hydroxyurea causes testicular failure.
Antiandrogens can affect sperm production as does ionising radiation - flutamide and cyproterone, spironolactone, ketoconazole
Environmntal factors - Pesticide, lead, cadmium and mercury, some insecticides and fungacides
Radiation
Smoking drops sperm count
Hyperthermia
Systemic disorders – sickle cell – cause cause testicular infarcts (also hypo hypo from iron overload)
CKD / cirrhosis / malnutrition
post testicular
Epididymis
Absence – CBAVD 82% of the time its CF gene
Infection / drugs or toxins can cause dysfunction
sexual dysfunction
vasectomy
Investigations
• semen analysis
2-7 days after sexual abstinence
Repeat testing should occur 3 months after the initial analysis to allow for the cycle of spermatozoa to be completed
If gross deficiency – repeat ASAP
Other investigations performed on the basis of clinical presentation
- karyotype
- Y chromosome microdeletion
- CFTR
- LH, FSH, total testosterone
- TSH, T4, prolactin
- FBE, ELFT, iron studies
Initial management
all males should receive the following advice:
- where applicable, cease recreational substance abuse, including alcohol and nicotine
- where applicable, reduce body weight to normal recommendations
- where applicable, optimal control of pre-existing medical conditions
- exercise in line with NHMRC recommendations
- commence a multivitamin preparation with appropriate antioxidants, such as vitamin C or E, as these have been associated with an increased chance of conception in assisted reproduction
- management of specific conditions is dependent on the clinical presentation
infertility basic hx for couples
Infertility is the absence of pregnancy after 1year of regular unprotected intercourse affecting 15% of couples
female Age Prev pregnancies + outcomes Prev fertility Tx / Ix and outcomes Gynae hx - cycles, molimina, STI, PID ? dysmenorrhoea (? endo) Med and surgical hx, prev tx abn smears NSAID use Sexual hx - frequency, function Medications Smoker Alcohol exercise occupation diet FHX prev birth defects infertility mental disability System review - sx thyroid disease, galactorrhoea, hot flushes
Exam
BMI + fat distribution
Signs turners (short, stocky, square chest)
Hirsutism, acne, thyroid,
Scars
Pelvic - adnexal masses, tender uterosacrals size uterus
Smear
Male
History
• Developmental history
• Testicular descent, pubertal development, loss of body hair, or decrease in shaving frequency
IQ help at school
• Medical history including Chronic medical illness and infections, such as mumps orchitis, sinopulmonarysymptoms,
sexually transmitted or genitourinary tract infections including prostatitis
• Procedures involving the inguinal and scrotal areas such as vasectomy, orchiectomy and inguinal hernia repair
• Drug and environmental exposures – alcohol, smoking, steroids, chemotherapy, drugs that raise prolactin, exposure to toxic chemicals, radiation, recreational drugs
• Sexual history: libido, frequency of intercourse, and previous fertility assessment
• School performance: history of learning disabilities suggestive of Klinefelter’s syndrome
Previous fertility hx - prev pregnancies
sexual function
relationship trouble
Examination
• general observation statue H W BMI eneral obs
• general appearance, including height, weight, blood pressure and pulse
Androgen deficiency:
• increased body fat and decreased muscle mass
• gynecomastia
STCR B
Tanner stage - pubic and axillary hair
External genitalia
• examination of the scrotum for absence of the vas, epididymal thickening, varicocele, and hernia
• Praderorchidometeror calipers
reflects decreased volume of the seminiferous tubules
• normal volume > 15 ml
Ddx 40 % mixed 25% unexplained - documented ovulation, thorough evaluation of tubal patency, normal cavity, semen analysis, oocyte reserve ovulatory disorders 25% tubal damage 20% male factor 30% uterine or peritoneal disorders endometriosis other
Principles
See couples together
written information
offer counselling as can be very stressful
Work up ensure ready for pregnancy cx screening antenatal bloods viral screen HIV hep B and C Immunity screen rubella and varicella
Semen analysis TSH prolactin D3 LH FSH E Midluteal progesterone Can do E and LH too
Anatomy
Pelvic USS
HSG (low risk hx and exam)
lap and dye if endo sx on hx
Assess ovarian reserve
+/- AMH
High prolactin
ddx MRI brain - stalk lesions, prolactinomas medication review - psych meds CKD - renal function hypothyroidism - TFTs
Review
visual fields
headaches
polyuria or polydipsia
Management stop treatment once pregnant Can decide to continue prn review each trimester dont measure levels
Macroprolactinaemia
15% enlarge and cause pregnancy problems
visual field assessment in pregnancy
If suspicion FU with MRI
Treatment is safe in pregnancy and can be used if tumor is expanding
(carbergoline has less side effects)
Safe in breast feeding but can be hard to initiate
Microprolactinaemia
stop when pregnant
POI
Loss of ovarian function before 40
Dx
FSH levels on 2 blood samples 4-6 weeks apart elevated >25IU/l under 40 year old
Causes
Genetic
Turners
Pre mutation FMR 1 gene (fragile X)
Not genetic Autoimmune syndromes Isolated Addisons Polyglandular syndrome
Ovarian toxins Chemotherapy Radiotherapy Galactosaemia Infection eg mumps
Surgery
Oopherectomy
Investigations Karyotype Premutation FMR1 gene ovarian / adrenal and thyroid autoantibodies – of positive then needs an ACTH stimulation test to exclude addisions DEXA scan
Management POI
Written information / support groups / psychological support / face to face consult, annual FU
Offer sex steroid replacement with a choice of HRT or a combined hormonal contraceptive to women with premature ovarian insufficiency, unless contraindicated (for example, in women with hormone-sensitive cancer).
the importance of starting hormonal treatment either with HRT or a combined hormonal contraceptive and continuing treatment until at least the age of natural menopause (unless contraindicated)
The purpose is cardiovascular and bone protection and reduced dementia risk
Oestrogen is best for vaginal atrophy
Androgen replacement is a treatment for sexual dysfunction recent guidelines suggest against DHEA use as lack fo efficacy and limited long term safety data
If E is contraindicated then SSRI SNRI and antiepileptics can be used to control menopausal sx
Screen for coexisting disease
Assess for thyroid disease
Assess for adrenal insufficiency
Managing long term risk
Inform GP
High risk Cardiovascular disease and reduced life expectancy
Smoking cessation Monitoring and treating blood pressure Diabetes Lipids Cardiac friendly lifestyle
Infertility
Information about spontaneous conception
50% intermittent menses
10% fertility
Oocyte donation is the best current option for fertility
Autosomal screening should be based on the age of the donor
Oocyte donations are high risk pregnancies
If Fhx of POI/ pregene mutation FMR1 then should have genetic counselling
If in a woman with turners, assess cardiac endocrine and gynaecology state before pregnancy
Reduced bone mineral density and increased fracture risk
secondary amenorrhoea
Bloods
FSH LH E P
Androgen panel
17 OHP
USS
Recurrent miscarriage
Hx - review Risk factors AMA Previous miscarriages and their management Obesity increases the risk of recurrent or sporadic miscarriage T2DM abnormal thyroid function PCOS thrombophilia Prev dx uterine abnormalities
Ddx
Antiphospholipid syndrome
Balanced structural chromosomal anomaly eg a balanced recipricol translocation or a robertsonian translocation
Anatomic factors
Uterus - septum or mullerian abnormalities
Cx weakness is associated with uterine malformation
Endocrine
T2DM
Abnormal thyroid function
PCOS
Thrombophilias
Investigations
Antiphospholipid antibodies
2 positive tests 12 weeks apart
Lupus anticoagulant (using the dilute russell viper venom time test + a platelet neutralising procedure) or anti cardiolipin IgM or IgG – titre over the 99th centile
Pelvic USS
Can use 2D USS or HSG as a screening test
3D USS or hysteroscopy laparoscopy for definitive dx
Karyotype
Cytogenics of third and subsequent miscarriages
Parents peripheral blood karyotype if recurrent miscarriages and POC reports unbalanced structural abnormality
Parental balanced chromosomal translocation
Thrombophilia screen
Factor V leiden
Prothrombin gene mutation
Protein S
Endocrine abnormalities
T2DM
Thyroid disease
Associated High BMI AMA Smoking Other factors
Treatment
If no cause found then TLC
Anti phospholipid syndrome
Antiphospholipid syndrome Positive 2 samples 12 weeks apart Anti B2 glycoprotein Anti cardiolipin Lupus anticoagulant
Obstetric outcome
3 or more consecutive pregnancy losses before 10 weeks
1 spontaneous morphologically normal pregnancy loss after 10 weeks
Preterm birth before 34 weeks owing to placental insufficiency Vascular dx
One thrombosis – superficial thrombophlebitis doesn’t count
Management in a specialist clinic
APS
Aspirin and heparin
Reduces miscarriage rate by 55%
Risks of heparin
Doesn’t cross placenta so no fetal risk
Maternal includes bleeding, hypersensitivity reactions, heparin induced throbocytopenia
WHen used long term – osteoperosis and vertebral fractures
LMWH is safe
Still at risk of repeat miscarriage, PET, IUGR and PTB
Don’t use steroids or IVIG
azoospermia
Differential Diagnoses:
Primary testicular dysfunction
Idiopathic; trauma; infection (ie mumps orchitis or HIV); neoplasm + chemotherapy + radiation
Obstructive
Congential (Klinefelter’s syndrome); iatrogenic (vasectomy); infective; CF (if vas absent)
Endocrine
Hypogonadotrophic hypogonadism
Autoimmune
Anti-sperm antibodies
Drugs/Medications
Recreational drugs: tobacco, ETOH and THC
Medications: anabolic steroids, sulfasalazine and antifungal agents; chemotherapy
Environmental
occupational exposure to head, radiation and chemicals
Varicocoele
Ix Assess post ejaculate urine STI screen FSH LH T Prolactin TSH Y chomosome microdeletions Karyotype CF screen Testicular USS
balanced translocation
genetic counselling
It is a inherited or spontaneous
transfer of genetic maternal from one chromosome to another
Effect depends on the genes are affected
Deficit can offer if
related to infertility or recurrent miscarriage
Reproductive options in couples with chromosomal rearrangements include proceeding to a further
natural pregnancy with or without a prenatal diagnosis test, gamete donation and adoption
Specific counselling on outcome depends on
Recurrent miscarriage
recurrent miscarriage
1% pregnancies
Psychological support written information and support groups
50% unexplained
Success is high
Antiphospholipid screen 2X 12/52 apart Lupus anticoagulant B2 glycoprotein IgG IgM Lupus anticoagulant anti cardiolipin IgM or IgG Genetic testing third POC - karyotype Parental karyotype if POC abnormal Pelvic USS 3d If T2 loss consider thrombophilia testing
Consider TFT and HbA1c
consider progesterone (RANZCOG GL says no metaanalysis says yes)
Anti phospholipid
Condition
Antiphospholipid syndrome is dx by the presence of specific antibodies in your blood one of lupus anticoagulant, anti cardiolipin antibodies and B2 glycoprotein
plus
either
3 miscarriages <10 weeks
one pregnancy loss after 10 weeks of a morphologically normal pregnancy
PTB before 34 weeks due to placental disease
OR venous or arterial Thrombosis
It is the most important treatable cause of recurrent miscarriage and the live birth rate with no treatment is very low
The risks are recurrent miscarriage, PET PTB IUFD and IUFD
Management
Obstetric led care
Aspirin + heparin
Fetal risks - nil - heparin doesn’t cross the placenta
Maternal risks - bleeding, hypersensitivity reaction, thrombocytopenia, osteopenia and fracture
uterine artery dopplers at 20 weeks
Serial growth scans
monitor urine dip and BP each visit
Ashermans syndrome
Ashermans syndrome is scarring of the endometrium
Hysteroscopy allows for assessment and treatment
Can be office hysteroscopy or GA by an experienced hysteroscopist
can be done under USS or laparoscopic guidance
recurrence 30-60%
No definitive way to prevent adhesions reforming
consider E therapy to prevent endometrial growth / intrauterine device to prevent immediate reformation of the adhesion
Pregnancy would be high risk needing obstetric led care risk involves IUGR PTB abnormal placentation
Primary amenorrhoea
Ix
Bhcg FBC U+E LH FSH E prolactin TFTs Androgen panel 17 OHP DHEAS SHBG Pelvic TV USS +/- MRI Karyotype Tumors Brain imaging
Secondary amenorrhoea
Ix
Bhcg FBC U+E LH FSH E prolactin TFTs Androgen panel 17 OHP DHEAS SHBG Pelvic TV USS
Progesterone withdrawal test to assess endometrium
Work up for POI
Karyotype
FMR1 gene
anti ovarian adrenal and thyroid antibodies
kallmans syndrome
Hypothalamic hypogonadism with anosmia
Autosomal dominant condition
More common in males than females
Commonest cause of isolated hypogonadotrophic hypogonadism
Associated anosmia secondary to defective development of olfactory bulb and tract
Note - present with delayed puberty but still get pubic hair (adrenarche) which differentiates them from those with constitutional delay
Management If not wanting to conceive Bone densitometry baseline Lifestyle measures Hormone replacement therapy with daily oestrogen and cyclical progestogen
If wanting to conceive
Complete fertility work up to ensure no other factors
Female - consider tubal patency
Male - history / exam / semen analysis, to ensure no male factor
Antenatal bloods
Commence folic acid and iodine
Ovulation induction with recombinant FSH or pulsatile GnRH use
Describe monitoring during ovulation induction cycle and possible complications
Ovulation induction with recombinant FSH
Aim of ovulation induction is formation of a single dominant follicle
Use COC to induce a withdrawal bleed and trigger start of cycle for timing
Daily rFSH / HMG at dose of 50-150iu for 3 - 5 days (depending on response)
Serum oestradiol and TV USS to assess follicle count and size 48 hrly
HCG trigger when follicle >18mm (corresponding oestradiol 200pg/ml)
Timed coitus - ovulation is typically 38-40 hours later
Consider luteal phase support with progeseterone
Ovulation rate ~72%, pregnancy rate 45%
Complications: Multiple pregnancy ~10-30%, OHSS ~ 5-15%
Ovulation induction with GnRH.
Use infusion pump which supplies pulsatile GnRH to mimic endogenous source. Resulting FSH/LH remain in normal range so complication risks above are very low. Do not need trigger as get endogenous LH surgery.
Do however require luteal support (HCG, progesterone, or continued GnRH)
Ovulation rates 90% with pregnancy rates 80%
Disadvantages are cost, maintaining the pump, and injection site.
how to treat anovulation
Patient discussion Risk OHSS Risk multiple pregnancy No evidence to support risk of adverse effects on long term ovarian function or reproductive neoplasia Contraindicated if BMI over 35
Options clomiphine - 80% ovulation 30-40% pregnancy in 6/12 Take for 5 days From day 2/3 of cycle Start 50mg Ovulate 7 days after the last tablet Can use for 6 cycles Can increase dose to 150 mg daily 7% multiple pregnancy rate. Hot flushes and breast tenderness. OHSS rare
letrazole - less multiples less side effects
Gonadotrophin
Metformin if impaired glucose tolerance
Next line Laparoscopic ovarian drilling
Describe IUI
Can be stimulated or unstimulated cycle
wash sperm of prostaglandin and semen protein and concentrate it so high numbers of motile sperm are high in the female reproductive tract - Timing should be based on LH surge
No clear data if one or two IUI in a cycle is better
Indicated for people who cannot have regular sex, either due to a physical disability, psychosocial problems donor sperm or same sex relationships
This is not a treatment for unexplained infertility, mild male factor or for mild endo
May work to improve live birth rate
If fails after 6 cycles, try another 6 (if tubal patency sperm quality and ovulation is normal)
Success 10-15% per cycle
This depends on age, ET, number of follicles, type of infertility
Risks infection and multiple pregnancy
Can Do IUI with ovulation induction - clomiphine is used but gonadotrophin has a high rate of multiple pregnancy
Risk of multiple pregnancy – if more then 3 dominant follicles then IUI is abandoned
fertility and endometriosis
Does treatment make a difference?
Surgical treatments Ablation vs resection resection Histological diagnosis Complete resection Reduction in residual non viable issue + then adhesion formation ? Lower recurrence
Aims – remove macroscopic disease and restore pelvic anatomy
Resection stage 1-2 disease is helpful for spontaneous conception
No data to say if exicsion helps ART
Stage 3 or 4 no difference - treatment would be for symptoms
Endometrioma
Spontaneous conception – reduced ovulation in an ovary with an endometrioma 30% vs 70%
Excision is better then drainage for pregnancy and recurrence
Post op hormones doesn’t make a difference for fertility
ART has worse outcomes if woman have endo
Communication station genetic carrier screening
how to explain
There are many hundreds of inherited genetic conditions that can affect human health, and most are very
rare. However, when all these inherited conditions are considered together, they affect up to 1 in 400
people. The majority of children born with such conditions are born into families with no other affected
family members. This occurs because a healthy couple can pass on genetic changes to their child without
knowing that they are carriers of that condition. The two major types of inheritance that can lead to a
healthy couple having children with serious genetic conditions are called autosomal recessive and X-linked
recessive.
In autosomal recessive inheritance, a person inherits a faulty gene from each parent. Genes are the
inheritance particles. We have about 23,000 pairs of genes, one in each pair inherited from each parent.
For an autosomal recessive condition, if a person has one faulty gene and one healthy gene, they will not
have the condition. They are a so-called “carrier” of the condition. We are all carriers of on average two
severe autosomal recessive conditions. It is only if both members of a couple are carriers of the same faulty
gene that there is a 1 in 4 chance of having a child affected by that condition. The most common types of
autosomal recessive conditions in our community are thalassaemia and cystic fibrosis.
X-linked inheritance is closely related to the sex of the individual, with males generally being more severely
affected than females. Genes lie on chromosomes, which can be thought of as long strings with the genes
as beads on the string. Males have an X and a Y chromosome whilst females have two X chromosomes.
When there is a faulty gene on the X chromosome, females are generally unaffected or more mildly affected
than males since they have a second unaffected copy of the gene. Males only have one X chromosome and
so if there is a faulty gene on their X chromosome they are more severely affected by the condition since they
do not have a second X chromosome to compensate. If a woman is a carrier for an X-linked condition, there
is a 1 in 4 chance of having an affected son with each pregnancy. The most common X-linked recessive
condition is fragile X syndrome.
Testing for inherited conditions
Babies are already tested for a large number of genetic conditions via the newborn screening ‘heel prick’
test. However, it is also possible to test healthy adults to see if they have an increased chance of having a
child with an autosomal or X-linked genetic condition before conception or birth. This is called reproductive
carrier screening. If both members of a couple are known carriers of the same autosomal recessive
condition or a woman is a carrier of an X-linked condition, there are a number of options available. These
options include:
1. Having a child naturally and testing after birth to see if the child is affected.
2. Conceiving naturally and having diagnostic testing during pregnancy to determine if the fetus is
affected. This is usually performed with an invasive test (amniocentesis or chorionic villus sampling).
3. Conceiving the pregnancy by in vitro fertilisation (IVF) and testing embryos by preimplantation
genetic diagnosis (PGD). Unaffected embryos would then be selected for achieving pregnancy.
4. Using donor sperm, egg or embryo from unaffected individuals.
5. Adoption.
6. Not having children.
Carrier screening can be performed at any time, but it is preferable to screen before a couple conceives so
that they have time to understand and consider their reproductive options, such as preimplantation genetic
diagnosis. The most common conditions for which carrier screening is available are thalassaemia, cystic
fibrosis, spinal muscular atrophy and fragile X syndrome.
There are some ethnic-specific patterns of genetic inheritance, which may lead to a specific offer of
additional testing. For example, couples of Eastern European (Ashkenazi) Jewish decent, may wish to have
carrier testing for Tay Sachs disease, Niemann Pick disease type A, Fanconi anaemia group C, familial
dysautonomia, Bloom syndrome, Canavan disease and mucolipidosis type IV in addition to screening for
thalassaemia, cystic fibrosis, spinal muscular atrophy and fragile X syndrome.
Reproductive carrier screening generally incurs out of pocket expenses where there is no family history of the condition. Where there is a family history of a genetic condition, referral to a clinical geneticist or genetic
counsellor may be indicated and testing for carrier status for the condition may be funded by the
government.
