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
