Fertility Flashcards
How common is subfertility?
• Subfertility is very common – with 1 in 6 couples seeking specialist help.
How likely is it a couple will conceive within 1 year? 2 years?
• People concerned should be informed that 80% of couples in general population will conceive within one year if:
o Woman <40, do not use contraception, regular sexual intercourse (every 2-3 days)
o About half will conceive in 2nd year
Causes of subfertility?
- Ovulation disorder (21%)
- Tubal factor (15-20%)
- Male factor (25%)
- Unexplained (28%)
- Endometriosis (6-8%)
- Sexual dysfunction (4-5%)
Causes of primary ovulation disorder infertility?
Premature ovarian syndrome
Genetic (Turner’s syndrome – 45X0; hypergonadotrophic hypogonadism)
Autoimmune
Iatrogenic (surgery, chemo)
Causes of secondary ovulation disorder infertility?
PCOS
Excessive weight loss or exercise
Hypopituitarism (tumour, trauma, surgery)
Kallman’s syndrome (anosmia; hypogonadotrophic hypogonadism)
Hyperprolactinaemia
Causes of tubal factor infertility?
o PID, pelvic infection, miscarriage o STIs o Female sterilisation o Bicornuate uterus o Fibroids o Hostile cervical mucous
Important points in female infertility history to consider in: General health Infertility history Menstrual history Sexual history PMH Drugs
General Health o Smoking (stop), alcohol (reduce), recreational drug (avoid), BMI (aim for normal)
Infertility History
o Age, duration of subfertility, coital frequency & problems, any previous pregnancies in either partner, Hx of ectopic/tubal/pelvic surgery
Menstrual History
o Menstrual cycle regularity and LMP (? pregnant), pelvic pain (dysmenorrhoea, dyspareunia)
Sexual History
o Cervical smear history, previous/current STI/PID
PMH
o Any relevant medical or surgical history, CKD, DM, anorexia
Drug history (any prescription drugs that may be contraindicated in pregnancy and recreational drug use)
Folic acid
Examination performed in infertility female?
General: BMI Signs of endocrine disorder: • Hyperandrogenism (acne, hairgrowth, alopecia), acanthosis nigricans, thyroid disease Visual field defects (?prolactinoma)
Pelvic:
Exclude obvious pelvic pathology (adenexal masses, uterine fibroid, endometriosis [painful fixed uterus], vaginismus)
Cervical smear
Chlamydia screening
When to offer investigations in subfertile woman?
• Offer investigation after 1 year of trying (earlier if female and >35, amenorrhoea, oligomenorrhoea, past PID, past cancer Rx)
Primary care investigations of subfertility?
o Chlamydia & Rubella screening
o Mid-luteal progesterone level (on day 21 of 28-day cycle, to confirm ovulation >30 nmol/L)
o Baseline (day 2 – 5) hormone profile including FSH (high in POF, low in hypopituitarism), LH
o TFT
o Prolactin
Secondary care referred indicated when?
o Refer when woman >36, known cause of infertility, Hx of risk factors, investigations show apparent no chance of pregnancy with expectant management
o Specialist clinic.
Investigations performed when assessing uterine/ovarian structure in female subfertility?
Pelvic USS
• Every woman – looks at uterus (shape, septum, endometrium, fibroids and polyps), ovaries (shape, present, PCOS)
Hysteroscopy
• If abnormal USS, gold standard for uterine anomalies
• Can look for fibroids, polyps, adhesions, septae
Investigations used when assessing tubal patency in female subfertility? How and when?
Hysterosalpingogram (HSG)
• Uses X-ray and contrast injected through cannula in cervix to demonstrate uterine anatomy and tubal patency
• Women with no known comorbidities (PID, ectopic pregnancy, endometriosis)
• Only perform if chlamydia swabs negative and give azithromycin 1g PO stat
Laparoscopy and dye test
• Day case procedure which can be combine with a hysteroscopy to assess the uterine cavity is necessary.
• Gold standard for tubal patency and used 1st when pelvic comorbidities (can be diagnosed and treated) and 2nd line if HSG abnormal
• Requires GA
What is ovarian reserve testing? When used?
• Ovarian Reserve Testing (Pre-IVF)
o Measured around Day 3 of menstrual cycle – predict likely response to gonadotrophin stimulation in IVF
o Anti-Mullerian hormone ≤5.4pmol/L low and ≥25pmol/L for high
o Total antral follicle ≤4 for low response and >16 for high response
o FSH >8.9 for low and <4 for high
Lifestyle modification in female subfertility?
Healthy diet, stop smoking/recreational drug, reduce alcohol consumption, regular exercise
Folic acid 0.4mg/d
- 5mg/d - previous child with neural tube defect, personal or family history of neural tube defect, DM1/2, coeliac disease, BMI >30, thalassaemia
Avoid timed intercourse (recommend every 2-3 days)
Avoid ovulation induction kits/basal temperature measurements (no evidence of success and stressful)
Vitamin D 10mcg/d
Psychological management of female subfertility?
- Subfertility and its management can be very distressing.
- Some treatments have side effects and are not guaranteed to be successful.
- The stress of this and disappointment of failed treatment needs to be addressed.
- Couples should be offered counselling before and after treatment, along with information regarding patient support groups
Ovulation induction techniques used in female subfertility?
Weight loss/gain as appropriate.
Anti-oestrogens (e.g. Clomifene 50mg days 2-6)
Gonadotrophins or pulsatile GnRH
Laparoscopic ovarian diathermy
Insulin sensitizers (Metformin)
Surgery
Assisted reproduction (IUI/IVF/oocyte donation)
When are ovulation induction agents used mostly?
PCOS
If ovulation at any time - await natural conception (IVF if no pregnancy in 6-9 cycles)
If no ovulation: Lose weight Clomifene GnRHs Laparoscopic ovarian diathermy Metformin used alongside
If no pregnancy in 6-9 cycles then offer IVF
Surgical management of female subfertility?
Preferably laparoscopic
Treat endometriosis (laser/diathermy/excision)
Tubal surgery (microsurgery/adhesiolysis)
How common is male subfertilty?
• Accounts for 20-25% of cases of subfertile couples.
How likely are a couple to conceive with 1 year? 2 year?
• People concerned should be informed that 80% of couples in general population will conceive within one year if:
o Woman <40, do not use contraception, regular sexual intercourse (every 2-3 days)
o About half will conceive in 2nd year
What is male fertility dependent on?
• Normal male fertility is dependent on normal spermatogenesis, erectile function and ejaculation.
Where does spermatogenesis take place? How? When?
• Spermatogenesis takes place in seminiferous tubules
o Undifferentiated diploid germ cells (spermatogonia) multiply and transformed into haploid spermatozoa
o Takes 74 days
o LH stimulates Leydig cells to produce testosterone
o Testosterone and FSH stimulate Sertoli cells to produce substances for metabolic support of germ cells and spermatogenesis
Causes of male infertility?
- General Health
- Semen abnormality (85%)
- Azoospermia (5%)
- Immunological (5%)
- Coital dysfunction (5%)
General causes of male infertility?
o Obesity impairs fertility
o Smoking
o Tight-fitting underwear affect semen quality
o Alcohol consumption
o Anabolic steroids, marijuana, opioids, cocaine
Semen abnormality causes of male infertility?
- Idiopathic oligoasthenoteratozoospermia (OATS)
- Testis cancer
- Drugs (inc. alcohol, nicotine)
- Genetic
- Varicocele
Azoospermia causes of male infertility?
Idiopathhic hypogonadotrophic hypogonadism (HH) Kalmann's, Klinefelter's Pituitary adenoma Anabolic steroid abuse Cryptorchism Orchitis Chemo-radiotherapy Congential bilateral absence of the vas deferens (CBAVD) Vasectomy STIs
Immunological causes of male infertility?
Antisperm antibodies
Idiopathic
Infection
Coital dysfunction causes of male infertility?
Erectile dysfunction
Ejaculation normal (hypospadias, phimosis, disability)
Retrograde ejaculation (diabetes, bladder neck surgery, phenothiazines)
Failure in ejaculation (MS, spinal cord/pelvic injury)
Key history parts of male subfertility?
General, infertility, sexual, PMH, Drug
• General Health o Smoking (stop), alcohol (reduce), recreational drug use (avoid), BMI (aim for normal)
• Infertility History
o Age, duration of subfertility, coital frequency & problems, any previous pregnancies in either partner
• Sexual History
o Previous/current STI, erectile dysfunction
• PMH
o Any relevant medical or surgical history, FHx, CKD, DM, anorexia
• Drug history
(recreational, steroids, alcohol, nicotine, marijuana, opioids)
Examination of male subfertility?
- Record BP, BMI
- Examine male secondary sex characteristics, gynaecomastia, hirtutism
- Site, consistency and volume
- Examine presence of varicocele, swelling, lymphadenopathy
When to offer investigations in male subfertility?
Offer investigation after 1 year of trying regular, unprotected sex
Investigations performed in male subfertility?
• Semen analysis (specimen produced by masturbation after 3 days abstinence from sex)
What parameters and normal values are there in semen analysis?
o Volume >1.5ml o Concentration >15 x106/mL o Total Motility >40% o Normal Forms >4% • Azoospermia = no sperm in ejaculate. • Oligozoospermia= reduced number of sperm in ejaculate (<15mil) • Asthenozoospermia (<32% motile spermatozoa) • Teratozoospermia (<4% normal forms)
When to repeat semen analysis?
Repeat abnormal test after 3 months
If two tests abnormal – further testing
What further investigations can be considered if abnormal male semen analysis?
o Screen for chlamydia
Hormone analysis
• FSH and testosterone (FSH increased in testicular failure)
Genetic testing (Karyotyping, exclude 47XXY)
Testicular biopsy
Cystic Fibrosis screen (CBAVD)
General management of male subfertility?
Treat any underlying medical conditions
Address lifestyle issues ( alcohol, stop smoking)
Review medications
• Antispermatogenic (alcohol, anabolic steroids, sulfasalazine)
• Antiandrogenic (cimetidine, spironolactone)
• Erectile/ejaculatory dysfunction (α or β blockers, antidepressents, diuretics, metoclopramide)
Medical management of male subfertility?
- Gonadotrophins in hypogonadotrophic hypogonadism
* Sympathomimetics (e.g. imipramine) in retrograde ejaculation
Surgical management of male subfertility?
- Relieve obstruction
- Vasectomy reversal
- Surgical treatment of varicocele does not improve pregnancy rate and is therefore not indicated.
Sperm retrieval techniques in male subfertility?
- From postorgasmic urine in retrograde ejaculation
* Surgical sperm retrieval from testis with 50% chance of obtaining sperm (greater is FSH is normal)
What assisted reproductive techniques can be used in male subfertility?
If sperm in ejaculate - ICSI and IVF
If no sperm in ejaculate - surgical sperm retrieval or donor sperm then IVF
General management of infertility?
Support and reassure Support groups and counselling may help Advice: Folic Acid supplements Regular 2-3 day sexual intercourse Reduce alcohol intake Stop smoking Optimise BMI
Treatment of hyperprolactinaemia in female infertility?
• Dopamine agonists (bromocriptine)
Define ART?
o Fertility treatments in which sperm and oocytes are handled with the aim of achieving pregnancy
Define IUI? When is it considered?
With partner or donor sperm (in natural or stimulated cycles)
Introduction of prepared (partner/donor) sperm into uterine cavity around ovulation
Considered when:
Difficulty having vaginal intercourse due to physical ailment or psychosexual problems
After sperm washing where the man is HIV-positive
Same-sex relationship
What is IVF? Indication?
o In Vitro Fertilisation and Embryo Transfer (IVF-ET, widely known as IVF) Indications may include: • Tubal disease • Male factor subfertility • Endometriosis • Anovulation • Women <40 should be offered 3 cycles • Women >40 offered 1 cycle if: o Never had IVF, no evidence of low ovarian reserve, discussed implications for IVF and pregnancy at this age
Success of IVF dependent on what?
Duration of subfertility
Age - 25-35
High AMH and FSH
Previous pregnancy
Reduced chance in smoking and high BMI.
What is the method of IVF?
- Ovarian stimulation with high dose gonadotrophins - multifollicular recruitment
- Prevent premature LH surge using GnRH analogues (agonists OR antagonists, depending on cycle)
- Follicles monitored by transvaginal USS
- Trigger final oocyte maturation - hCG, GnRH agonist
- Transvaginal oocyte retrieval by US guided needle aspiration (36 hours later)
- Sperm sample collected (or thawed if frozen), prepared and cultured with oocytes overnight.
- Fertilization checks of embryos
- Embryo transfer by a fine catheter through cervix on day 2-3 (cleavage stage)
- A maximum of two embryos are US transferred in women under 40.
- Pregnancy test 2 weeks later
What is pre-implantation genetic diagnosis?
- Aims to reduce the recurrence of genetic risk in couples known to carry a heritable genetic condition.
- Many couples are fertile, but IVF allows embryo biopsy, single cell diagnosis and the transfer of unaffected embryos to the woman.
- Biopsies are usually done at cleavage stage and PCR or fluorescent in-situ hybridisation (FISH) used for genetic diagnosis.
Define ICSI?
A single sperm is injected into the ooplasm of the oocyte - then IVF
Used for men with severely defects in sperm quality, obstructive/non-obstructive azoospermia and failed IVF treatment
What is donor insemination?
Azoospermia, deficits in semen quality which don’t want ICSI, high risk of transmitting genetic/infectious disorder, Rhesus isoimmunisation]
What is oocyte donation? Indicated when?
May offer a chance of pregnancy for women previously considered to be irreversibly sterile
Indicated in:
• Premature ovarian failure, Turners syndrome, bilateral oophorectomy, following chemo/radiotherapy, IVF failure
• Older women >45
Risk of: preterm birth, low birth weight
What is IVF surrogacy? Method?
IVF surrogacy
The couple who want the child provide both sets of gametes
Following IVF the embryos are transferred to the surrogate
Indications include women who have congenital absence of the uterus (Rotinkansky;s syndrome), following hysterectomy, or with severe medical conditions incompatible with pregnancy.
What is natural surrogacy?
The surrogate is inseminated by the sperm of the male partner of the couple wanting the child
Other options for ART?
Adoption and fostering
Complications of ART?
o Multiple pregnancies
o Higher risk of preterm birth
o Ovarian Hyperstimulation syndrome
Cause of OHS?
Systemic disease and VEGF cause pathology
• Causes capillary permeability and fluid shifts into third space compartments
risk factors for OHS?
- PCOS
- Age <30
- Use of hCG for luteal phase support
Symptoms of OHS?
- Symptoms start 24h after hCG administration but severe in 7-10 days
- Ovarian enlargement
- Ascites
- Nausea and vomiting
- Pleural effusions
- Hypercoagulability
Management of mild OHS?
o Outpatient – analgesia (AVOID paracetamol), restrict fluids, avoid strenuous activity and intercourse, avoid hCG
o Review by assisted conception unit every 2-3 days
Management of severe OHS?
o Admit o Analgesia and antiemetics o Daily U&E, LFT, FBC, albumin o Strict fluid balance o VTE prophylaxis o Paracentesis o May need ITU
Fertility preservation in females?
GnRH analogues for ovarian suppression
Oocyte cryopreservation
Social egg freezing
Fertility preservation in men?
Advisable before chemo, radio, surgery on testicle or reproductive tract
Sperm cryopreservation - in post-pubertal boys
Management of premature ovarian insufficiency?
Oocyte donation
HRT
Define Group 1 female infertility causes?
Hypothalamic pituitary failure (hypothalamic amenorrhoea, hypogonadotrophic hypogonadism)
Define Group 2 female infertility causes?
HPO dysfunction (PCOS)
Define Group 3 female infertility causes?
Premature ovarian failure (loss of ovarian activity <40)
Criteria: oligo/amenorrhoea >4 months and elevated FSH
FSH and estrogen levels in group 1, 2 and 3 female subfertility causes?
Group 1 - Low/Normal FSH, Low Estrogen
Group 2 - Normal FSH, Normal Oestrogen
Group 3 - High FSH, Low Estrogen
Define azoospermia?
Absence of sperm
Define oligozoospermia?
Low sperm count
Define asthenozoospermia?
Poor sperm motility
Define teratozoospermia?
Morphological defects to sperm
