Subfertility Flashcards
What is subfertility?
Inability to conceive after 1 year of unprotected intercourse
Primary = never been pregnant
Secondary - been pregnant before
Statistics of subfertility
80% couples conceive <12 months
90% within 2 years
10-15% British couples affected by subfertility
Fecundity (probability of conceiving each month) reduces with age
Causes of subfertility
Many couples have both M&F factors
15% idiopathic
Female factors of infertility
1) Tubal problems: 20%
- PID, ectopic, endometriosis
2) Chlamydia
- Can cause PID
3) Endometrioma
- Presence of endometrial tissue in and on ovary
- Affects 17-44% people with endometriosis
4) Fibroids
5) Polyps
- overgrowth of enometrial cells can cause infertility if they disrupt the uterine lining and impede implantation
6) Anovulation (25%)
- Ovaries do not release oocyte during mestrual cycle
7) Uterine anomalies - Congenital or acquired
- Failure of Mullerian duct fusion resulting in uterine malformations e/g/ bicornate uterus and uterine septum
- Ashermann’s syndrome
- Fibroids
8) Cervical anomalies - Infection, surgery
Categories of anovulation
WHO classifies anovulation based on serum gonadotrophin levels (FSH and LH)
WHO 1: hypogonadotrophic hypogonadism
- Causes amenorrhoea, low body weight, galactorrhoea
- Low FSH, low LH, low oestroadiol, high prolactin
- Due to inadequate GnRH secretion from pituitary or problem with hypothalamus
WHO 2: normogonadotrophic normoestrogenic
- Oligo or amenorrhoea, high body weight, hirsutism, acne
- Most common, most commonly due to PCOS
- Diagnosis according to revised Potter criteria: oligo/ anovulation, hyperandrogenism, PCOS on USS
- FSH and LH in normal range, high LF:FSH ratio, high testosterone
WHO 3: hypergonadotrophic hyperoestrogenic
- Usually an indication of ovarian failure, presents with hot flushes
- High LH, high FSH, low oestradiol, high TSH and low T4, Tuner’s syndrome, fragile X
Causes: genetic (Tuner’s), xRT, smoking
Most common cause of female infertility?
Anovulation - age and PCOS most common in UK
In the world it is tubal disease
Management of anovulation
WHO 1: weight gain, indice ovulation, treat prolactinoma with bromocriptine
WHO 2: lose weight, induce ovulation, ovarian drilling
WHO 3: HRR, donor oocytes needed if patient wants to undergo fertility treatment
What is a hysterosalpingogram?
Infection of radio opaque dye into cervix
Normal reult shows filling of uterine cavity and filling of fallopian tubes bilaterally
How can chlamydia cause infertility?
Infection can spread and cause PID
Fitz-Hugh-Curtis syndrome can also occur where PID causes swelling of the tissue around the liver
Types of fibroids
Intramural: most common, inside muscle
Subserosal: outside womb into pelvis
Submucosal: grow into womb cavity
Submucosal fibroids can affect fertility but unlikey that subserosal will
Investigations for subfertility
General: BMI, signs of PCOS
Pelvic examination: massess, endometriosis (fixed + painful uterus), cervical smeal, chlamydia screen
Urinary LH: + test indicates imminent ovulation
Baseline (cycle day 2-5) hormone profile
Mid luteal progesterone to confirm ovulation
Secondary care: transvaginal USS to look for PCOS, fibrids, endometriomas
Hysterosalpingogram
Trend of male sperm over the last 50 years
Parameters have been declining over the last 50 years and sperm of aging men have serious health implications for children
Oxidative damage to sperm DNA
Increased neurological conditions: sutism, BPD
Cleft palate, diaphragmatic hernia, heart malformations
Terms used to describe sperm parameters
Aspermia = absence of sperm
Azoospermia = absence of sperm
Oligozoospermia = low sperm count
Asthenozoospermia = poor motility
Teratozoospermia = morphological defects
Causes of male subfertility
Semen abnormality = 85%
- low count, poor motility, morphological defects
- Testicular cancer, drugs/ alcohol, varicocele
Aspermia = 5%
- Pretesticular: anabolic steroid use, idiopathic hypogonadotrophic hypogonadism, Kallman’s, pituitary adenoma
- Non-obstructive: cryptochordism, orchitis, Klienfelter’s, chemo, xRT
- Obstructive: congenital bilateral absence of vas def (CF), chlamydia, gonorrhoea
Immunological
- Antisperm antibodies/ infection
Cortical dysfunction
- Mechanical cause with normal sperm function e.g. hypospadias, phimosis, retrograde ejactulation, failure to ejactulate
Causes of retrograde ejaculation
DM, spinal cord injury, phenothiazines
WHO criteria of normal ejaculate
Volume >1.5mL
Concentration >15x10*6/mL
Progressive motility >32%
Total motility >40%
Normal morphology >4%
What is Kartagener’s?
Rare, autosomal recessive genetic ciliary disorder comprising the triad of situs inversus, chronic sinusitis, and bronchiectasis
Consider in a patient with hx of sinusitis, ear infections and bronchitis
Process of semen analysis
Male provides sample after 2-4 days no ejaculation
If any of the WHO criteria re abnormal second sample given 3 months later to exclude temporary illness
66% time no cause is found
Investigations for male infertility
FSH elevated: testicular failure
Karyotype: exlude Klienfelter’s
Cystic fibrois screen
Semen fructose test: fructose is sperm food, no fructose suggest obstruction
Low LH and low testosterone = hypogonadotrophic hypogonadism - MRI done to rule out lesion in hypothalamus or pituitary
Doppler: varicocele
What is Klinefelter’s?
47 XXY
Males who have an additional copy of the X chromosome
Primary features = infertility
Can also cause less body hair, breast growth
Weak muscles as babies and children
Broader hips
Associated with learning difficulties
What is Kallmann syndrome?
Defined by delay/ absence of puberty + anosmia
Due to isolated FSH/ LH deficiency - failed GnRH activity
More common in males but also occurs in females
Medication to induce ovulation
1) Clomifene citrate: antioestrogen, blocks negative feedback of oestradiol to pituitary thus increasing FSH secretion and folliculogenesis
2) Metformin: insulin sensitiser, reduces insulin levels, androgen levels, increases ovulation rates when combined with clomifene citrate
3) Letrozole: aromatase inhibitor, decreases oestrogen production by ovarian granulosa cells therefore decreases negative feedback on pituitary and increases FSH production and folliculogenesis
4) hMG or FSH + LH: gonadotrophins, stimulates folliculogenesis
5) Ovarian drilling: diathermy, enables spontaneous ovulation
Surgery to treat infertility
Tubal surgery offered to women >37yrs with mild tubal disease
Women with moderate - severe tubal disease are referred for assisted conception
- Hydrosalpinges (fluid in tubes) removed 1st)
- Ablation of endometriosis deposits
Treatment of male inferility
IVF/ ICSI
MESA: microsurgical epididymal sperm aspiration
PESA: percutaenous
TESE: testicular sperm extraction
TESA: percutaneous testicular sperm aspiration
How is PCOS-related subfertility managed?
Ovarian drilling if clomifene citrate not working
What is super ovulation/ controlled ovarian hyperstimulation?
Process used to promote release of >1 egg per month
Used for women with hypogonadotrophic hypogonadism or PCOS
Daily injections of FSH from day 3-5 promotes follicle growth
When biggest follicle reaches 17mm an injection of hCG given to induce ovulation + planned intercourse
What is the single most important predictor of IVF success?
Woman’s age
Most centres in the UK don’t go above 43yrs with number of embyros transferred based on age
<37: 1-2 depending on attempt
37-39: 1-2 depending on attempt
40-42: 2
Stages of IVF
1) Ovarian hyperstimulation: GnRH agonist used to achieve pituitary down regulation and promote ovulation. Daily FSH or hMG (LH+FSH) to promote follicular development. Pelvic USS from day 8 then every 2 days after to look for follicles, hCG injection given when lead follicle = 18mm
2) Oocyte recovery: USS guided transvaginal oocyte recovery is carried out 34-36hrs after hCG administration
3) Insemination: on day of oocyte recovery the male given semen sample which is added to petri dish with oocyte and 50-70% are fertilised within 24hrs
4) Embryo culture and transfer: 1-2 fertilised oocytes selected for transfer, the rest are frozen
Day 3-5 1-2 embryos are transferred to uterus under USS
5) Luteal phase support: progesterone supplementation used to support the pregnancy until 10 weeks when placenta starts to make own progesterone
How is ICSI different from IVF?
ICSI: sperm injected into egg rather than letting them do their thing in the petri dish
ICSI is used in 50% IVF
What is pre-implantation diagnosis?
1-2 cells removed from each embryo and genetically tested to screen for disabling conditions
Risks of IVF
Risks to mother
- Ovarian hyperstimulation syndrome: affects 7%, 1% severe
RFs: low BMI, PCOS, young
Usually presents 2-3 days after oocyte recovery, associated with capillary leakage leading to pleural effusion, pericardial effusion, ascites, intravascular volume depletion
Treatment: fluids, thromboprophylaxis, fluid drainage
Foetus: increased risk of multiple pregnancy
Success rate of IVF
25% overall
32% if <35
IVF in layman terms
Suppress normal cycle then stimulate ovaries via daily hormone injections
When ovaries look ready a final injection given to make eggs mature
Eggs collected and mixed with sperm
Fertilised egg implanted into womb
Any spares are frozen
What can be measured @ day 28 of the cycle to check if woman has ovulated?
Progesterone
