Fertility and early pregnancy Flashcards
Recurrent pregnancy loss investigations:
- Maternal and Paternal peripheral blood karyotyping
- Maternal Antenatal Screen including Hep B, C and HIV
- Lupus Anticoagulant, Anticardiolipin Antibodies (if above 20, please repeat in twelve weeks time) and anti-B2 glycoprotein - Antiphopholipid screen
- Thrombophilia screen: Factor V Leiden and protein S deficiency
- Thyroid Stimulating Hormone
- Day 2 or 3 menses FSH (with Estradiol level)
- HbA1c
- 3D Transvaginal ultrasound of pelvis
Neonatal heart block with Anti-Rho in SLE or APLS:
Weekly doppler from 16 – 24 weeks for USS if bradycardia heard
USS to look for AV dissociation in M-Mode
Refer to MFM – Dexamethasone and Salbutamol. have some evidence. 50-60% require cardiac pacemakers.
Complete heart block is HR <55 and can warrant immediate delivery.
SLE management of pregnancy:
MDT care in tertiary centre for pregnancy and delivery
Normal folic acid and iodine and vitamin D (increase folic acid if on antifolate meds)
First trimester screening or NIPT
Iron supplementation
Aspirin and clexane
Investigation of renal function with cell casts, 24 hour protein, renal USS +/- biopsy
Monthly monitoring of disease activity throughout pregnancy with FBC, U&E, Crt, LFT, anti DNA, complement titres, uPCR each trimester
Fetal surveillance: Weekly FHR 16-24 weeks +/- echo to detect heart block, uterines at anatomy, umbilical dopplers from 24 weeks, serial growth scans
Heart block – refer MFM, consider treatment with dexamethasone, salbutamol for heart failure
Flares treated with steroids +/- NSAIDs, azathioprine (no role for prophylactic use)
If on long term steroids then need IV hydrocortisone, monthly MSU’s to monitor for infection, several GTT for increased risk GDM
Intrapartum: CS routine indications, deliver by term, CEFM, stress steroid PRN, not for ergometrine
Postpartum: VTE prophylaxis, monitor baby, not for COCP
Male factor infertility history: Pregnancy Testes Sex Drugs (smoking and alcohol)
• Ever fathered a child
• History surgery, orchitis (Mumps/TB), torsion, vasectomy, radiation , chemotherapy, exposure to toxic substances with work
• No sexual dysfunction , nil erective or ejaculatory difficulties
- Smoking, alcohol and drugs (Steroids, Anti-depressants e.g. fluoxetine, Anti-epileptics e.g. lamotrigine, Anti-hypertensives e.g. nifedipine, Chemotherapy drugs, Sulfsalazine or Risperidone)
Male fertility investigations:
Repeat semen analysis 3 months later
karyotype – 46XY
Y chromosome micro-deletions AZF mutations
CF screen – negative
Hormonal profile – LH, FSH Testosterone, prolactin, TFT
Testicular ultrasound
Post ejaculation urine sample (retrograde ejaculation)
Sperm antibody test significant if >40%
Azoospermia (absence of sperm in ejaculate)
- Would suggest testicular needle Biopsy
- May be done under local or GA
- If sperm found would consider freezing sample as back up
- Would require IVF/ ICSI for fertility
Fertility regime that increase risk of OHSS
Use of GnRH agonist rather than GnRH antagonist
Exposure to HCG (as trigger or luteal support)
High-dose gonadotropin stimulating reigmene
Multiple follicular response with stimulation
Conception / becoming pregnant
- Fresh embryo transfer rather than elective cryopreservation
Number of oocytes retrieved in IVF
· Risk increases with increasing number
Management of OHSS
Admit
Strict Fluid Balance and Daily Weight, abdominal girth – concern is for hypovolemia secondary to third spacing
Daily FBC, U&Es, Creat, RFT, HCT
CXR, VGB
IV Fluid, treat antiemetics, pain relief – supportive cares
Monitor for signs of deterioration e.g. increasing SOB.
Consider albumin
Clexane + TEDs
Analgesia, avoid NSAIDs
Ensure appropriate place of monitoring e.g. on ward or ICU/HDU
Discuss severity
Drainage of pleural effusions and ascites
Causes of hydrops
Cardiac
Anaemia
Unexplained
Structural
Twins
Infection
Chromosomes
90% are non immune. NIHF has an obvious poor prognosis for the fetus, but can also have maternal
consequences as well with a 10% incidence of Mirror syndrome.
Aneuploidy = Most common cause of NIHF under 24/40 Cardiovascular abnormalities , Structural = Most common cause of NIH over 24/40
History, investigation of hydrops
History: Personal and family history to look for inheritable disorders associated with: • Alpha thalassemia • Metabolic disorders • Genetic syndromes • Infectious exposures • Parvovirus • Consanguinity Investigation: Detailed ultrasound • anatomy • MCA PSV • echocardiogram Mother • Blood group and RBC antibody screen • Baseline BP and urinalysis • FBC and film screen for thalassemia • Parvo, toxo, rubella, syphillis, • HSV(if recent primary infection) • Kleihauer-Betke Infant • Amniocentesis Karyotype PCR for TORCH pathogens Storage for further testing • Cordocentesis RBC for anaemia metabolic/genetic tests
Investigations for late IUFD
Kleihaur
Lethal feto-maternal haemorrhage is a cause of IUFD. Also fetal cells rapidly disappear so needs to be done ASAP. If rhesus negative 2 samples need to be sent one after the administration of anti-D to ensure adequately dosed to not impact future pregnancies.
Maternal bacteriology: - Blood cultures - MSU - Vaginal swabs - Cervical swabs Maternal bloods: FBC, LFTs, renal function & CRP Pre-eclampsia and its sequalae. Maternal sepsis, placental abruption and pre-eclampsia increase probability of DIC so include clotting screen.
Random blood glucose and HbA1c
May have occult type 1 or type 2 diabetes. GDM return to normal glucose a few hours after birth and may have a normal HbA1c. They would need specialist intensive clinics and growth scans and have increased risk of stillbirth would affect pregnancy next time and potentially have non pregnant consequences to health additionally.
Antibodies on group and screen
To rule out hemolytic disease
Urine for drug screen
Cocaine can be associated with IUFD secondary to abruption and would be metabolised if not measured now.
Maternal Coagulation profile and plasma fibrinogen
Can cause DIC 10% in first 4 weeks after diagnosis of stillbirth important to make sure she is currently stable
Maternal serology for viral infections, syphilis +/- tropical infections if needed
If she has evidence of a specific infection may need to protect staff and family members while caring for the woman and infant. Can confirm with booking serum results.
General preconception advice
Folic acid 800mcg (high dose in Anti-convulsants, diabetes, previous child or family hx of NTD or BMI >30 5mg)
Iodine 150mcg
400IU Vitamin D
Vegan/vegetarian Vitamin B12
Booking bloods - FBC, group & antibody screen, rubella, syphillis, MSU, Swabs, HIV, Hep B & Hep C and varicella.
- Avoid potential teratogens e.g. smoking, alcohol
- Gestational weight gain and optimise BMI
- Influenza, COVID and pertussis vaccinations
Screening tests: MSS1 10-13 weeks, MSS2 14-20 weeks and NT scan, NIPT ~10 weeks.
Anatomy scan ~20 weeks
OGTT 26-28 weeks (unless high risk 16 weeks)
Macroadenoma management in pregnancy
- perform neuro exam including visual fields
- arrange rpt MRI to assess for tumour enlargement
- ensure MDT input including MFM, obs physicians and neuro
- continue bromocriptine
- Pituitary apoplexy – occurs in 8% of patients with macroadenoma. Can cause life threatening hormonal and biochemical disturbance. Check TFTs, cortisol, ACTH, IGF, and urinary free cortisol. May need steroid replacement.
- Transsphenoidal surgery to resect tumour usually best performed in second trimester.
- discuss ongoing pregnancy care under high risk obs, give advice about fetal movements and side sleeping
- recognize breastfeeding will be CI with dopamine agonist
- Repeat all endocrine bloods 6-8 weeks post partum and arrange endocrine and neurological follow up
Testicular Examination
- Virilisation
- Testicular volume
- Vas deferens palpable bilaterally
- Any evidence of previous surgery, hernia
- Contour of tests regular
Investigations for Azoospermia
- Karyotype
- Y chromosome micro-deletions
- Cystic Fibrosis screen
- Hormonal profile: LH, FSH, Testosterone, prolactin and TFT
- Testicular USS
Fetal risks from Warfarin
- Teratogen; overall risk of embryopathy 10%
- Greatest risk between week 6-12 weeks
- Most common abnormality nasal/limb hypoplasia, less commonly CNS abnormalities; miscarriage; fetal bleeding at any stage in pregnancy
Secondary infertility
- Pelvic USS
- Day 2 -4 FSH (normal 4-10), LH (normal 4-10), estadiol and prolactin. Repeat all if raised. If repeat FSH >10 – primary ovarian insufficiency
- Total testosterone, sex binding globulin
- TSH
- DHEA, DHEA-S, 17-OH-progesterone (if raised exclude adrenal/ovarian tumour, late onset CAH or Cushing’s)
Fibroids and infertility
Fibroid positioning appears to influence fertility therefore imaging such as MRI should be used to exclude uterine cavity involvement.
Subserosal - no significant effect
Intramural - reduced fertility and increase in miscarraige rate
Submucosal - reduced fertility and increased miscarriage rate.
Indications for myomectomy in infertile women:
• ART with submucosal fibroids
• Infertile women who are symptomatic with fibroids
• Couples presenting after multiple failed cycles of ART where the female has intramural fibroids.
Lifestyle factors contributing to low sperm count
Alcohol Smoking Environmental exposure such as pesticides Tight underwear or shorts e.g. cycling shorts Drug use Increased BMI Saunas ++ Work related exposure
Kleinfelter’s XXY 1:660 men
Born with extra X chromosome sporadic not inherited
Taller (esp arms and legs), broad hips and gynecomastia and infertility.
Would need ICIS or donor sperm and IVF
Male factor sperm disorders
Oligospermia - a reduction in concentration <15million/ml
Azoospermia - no sperm in ejaculate
Asthenozoospermia - a reduction in motility <32%
Tetatozoospermia - reduction in normal morphology <4%
Normal sperm count
Morphology 4% Progressive motility 32% Total motility 40% Sperm count 39million per ejaculate Concentration 15 million per ml Vitality 58% Volume at least 1.5ml
OHSS explanation
It is a disease from vasoactive products released by stimulated ovaries which causes increased capillary permeability and third space fluid accumulation. It is usually self limiting and the majority of women usually have a resolution of symptoms in 7-10 days. Severe OHSS occurs in 3-8% of cycles and may require admission but majority of cases managed as an outpatient.
Severe OHSS
clinical ascities Oligouria <30ml/hr Heamatocrit >0.45 Hyponatraemia Hypo-osmalality Hyperkalaemia Hypoproteinaemia Ovarain size >12ml
Patient risk factors for OHSS
Young age Diabetes Multiple pregnancy PCOS Previous OHSS
Macroadenoma management in pregnancy
Perform neuro exam including visual fields
Arrange MRI to assess for tumour enlargement
MDT MFM, obs med and neurology
Continue bromocriptine breastfeeding contraindication
Repeat all endocrine bloods 6-8 weeks post partum
WHO classification secondary amennorhoea
Class 1 - hypogonadotropic hypogonadal anovulation
DDx: Anorexia, over excercising, Kallman’s, sheehan’s
Class 2 - Normogonadotropic normoestrogenic
DDx PCOS, obese or hereditary
Class 3 - Hypergonadotropic hypooestrogen
DDx POI
Total testosterone x2 higher
Virilization present
Raised 17-0h-progesterone and DHEAS
Exclude ovarian or adrenal ca
Late onset CAH
Cushings
Secondary amenorrhea and high prolactin
Ensure TSH has also been done (can be a/w thyroid)
Always repeat can be high in stress
Consider CT or RMI to look for micro/macro adenoma of the pituitary
Refer neurology or neurosurgery
Premature ovarian insuffiency
Women under 40 with 6 months amennorhoea and x2 FSH >40 at least 4 weeks apart Causes: - Idiopathic - Chromosomal e.g. turner's, fragile X, translocation - 46 XY gonadal dysgenesis - Iatrogenic e.g. Chemo/radio - Autoimmune e.g. thyroid or diabetes Additional tests: - USS - Lipids, BP and HbA1c - Karyotype - AMH - 2 yearly DEXA scan Management: - Education and counselling and psychological input - HRT - Fertility
Fertility options in POI
Egg donor IVF
Ovulation induction
Continue trying 5% with normal chromosomes ovulate
Surrogacy or adoption
Kallman syndrome
Idiopathic hypogonadotropic hypogonadism with anosmia (no smell)
Isolated deficiency in GnRH
Present with delayed puberty but still have normal puberty hair development
More common in males
Autosomal dominant
Management:
- Bone density
- Lifestyle measures
- HRT for secondary sexual characteristics
- fertility ovulation induction with recombinent FSH or pulsatile GnRH use
Cushing’s
A group of symptoms caused by too much cortisol likely secondary to a tumour in the adrenal or pituitary or long term corticosteroid use.
Symptoms:
- weight gain e.g. buffalo hump
- moon shaped face
- Striae
- Irregular menses
- Hirsuitism
Diagnosis:
Raised 17-OH-progesterone
Raised urinary cortisol >250nm/L
Overnight dexamethasone suppression test 1mg at 11pm and check cortisol at 8am result should <140nmol/L
Most likely infertile and need correction with surgery or stopping medication
PREGNANCY RARE
Increased fetal loss, prematurity and perinatal mortality
Neonatal adrenal insuffiency
Gestational diabetes
Maternal GDM and severe PET
Women with previously treated Cushings do well in pregnancy
Male Factor history PTSD
Pregnancy - ?any other children
Testes - surgery infection chemo or work
Sexual dysfunction
Drugs - smoking/alcohol/steroids/anti-depresssants
Management of Azoospermia
Suggest testicular needle biopsy
Local or GA
Sperm found freeze
Would then require IVF or ICIS
Molar pregnancy
Partial molar: Dispermy triploid P57+ve
Complete molar: Only paternal chromosomes
Should proceed for ERPOC
Increased risk of bleeding so consider the following: FBC and Group & screen
Senior SMO
Oxytocin
TXA
USS guidance
POC to lab for histopathology
Follow up with results
Diagnosis go to MDM or registry
t-HCGs weekly till negative then 3 negatives - partial
t-HCGs weekly till negative then 3 negatives then monthly for 6 months - complete
Contraception - avoid new pregnancy as it masks recurrence
COCP/condom/POP fine
IUD once HCG negative and menses return to avoid risk of perforation
Next pregnancy:
Early USS 6-8weeks + mid-trimester review to ensure to molar tissue
Future pregnancies t-HCG 6 weeks afterwards
Risk of recurrence 1:70
Persistent or change into malignant disease:
5% partial
20% complete
GTN
Criteria for GTN Plateau +/- 10% that lasts for 4 measurements Rise of t-HCG 3 measurements HCG >20,000 >4 weeks after evacuation Refer to GONC Staging investiagtions: tHCG, FBC, U&Es, TFTs and Co-ags CXR and CT-CAP FIGO staging 0-4 ERPOC repeat 4 or more chemo methotrexate
