Subfertility, spermatogenesis Flashcards
Requirements for conception
Progressively motile normal sperm able to reach and fertilise oocytes
Timely release of a competent oocyte
Free passage through vagina, cervix, uterus and fallopian tube for sperm to reach oocyte
Mature endometrium for implantation
Infertility
Inability to conceive after a period of time of frequent, unprotected intercourse requiring investigation and possible treatment
Affects 1 in 6
General causes of infertility
Unexplained Ovulatory Male factor Tubal abnormality Endometriosis
Indications for referral or investigation in women
Aged over 35
Amenorrhoea/oligomenorrhoea
Previous PID/STD
Abnormal abdo/pelvic examination
Indications for referral or investigation in men
Previous genital pathology
Previous STD
Significant systemic illness
Abnormal genital examination
Semen analysis
Sperm count>15 x 10^6/ml Motility >40% Morphology >4% Vitality >58% Volume 1.5-6.0ml
Abnormal semen analysis
Testicular failure
Obstructive or non-obstructive azoospermia
Y chromosome microdeletion
Cystic fibrosis - congenital bilateral absence of vas deferens
Female assessment
Screen for chlamydia and rubella
Ovarian reserve - LH, FSH, oestradiol, AMH, AFC
Ovulation tests - day 21 progesterone, LH surge testing kits
Tubal test
AMH in males
Produced by sertoli cells until reproductive maturity due to testosterone and FSH production
AMH in females
Produced by granulosa cells until early antral stage
Measures of ovarian reserve and response to ARTs
Increased AMH = Increased AFC = Increased OR
Causes for anovulation
- PCOS - normal FSH, LH and E2
- POF - high FSH and low E2
- Hypogonadotrophic hypogonadism - low FSH, LH & E2
Monitoring ovulation
Basal body temperature
Ovulation(LH) testing kits
Day 21 Progesterone/follicular tracking (USSS)
Hypogonadotrophic hypogonadism
complete shut down of ovaries as pituitary is not producing gonadotrophins
Causes of abnormal tubal patency
PID due to chlamydia Septic abortion Ruptured appendix Previous pelvic surgery Ectopic pregnancy
Imaging for tubal patency
Hysterosalpingogram HSG
Hysterosalpingo contrast sonography (HyCoSy)
Laprascopic dye
HSG
Hysterosalpingogram
X-ray imaging of the uterine cavity and fallopian tubes using a dye
Performed 2-5 days after menstruation
Advantages: relatively safe, easy to use, clear delineation of uterine cavity and fallopian tubes
Disadvantages: unable to assess pelvic peritoneum
Ideal imaging for most women
HyCoSy
Hysterosalpingo contrast sonography
Speculum inserted into vagina with catheter, water then dye injected to check fallopian tube patency and check uterus during ultrasound scan
Disadvantages: time consuming and requires training
Used in fertility clinics rather than NHS
Laprascopic dye
GOLD STANDARD
Need to screen for chlamydia
Advantages: live imaging of uterus and fallopian tube with greater sensitivity and specificity, used to diagnoses adhesions and endometriosis
Disadvantages: Invasive procedure
Induction of ovulation
Clomifene/clomiphene (oestrogen receptor blocker to increase FSH)
FSH and LH injections (FSH for a few days to develop follicle then LH for ovulation)
Use of FSH and LH injections for ovulation induction
If resistant to clomifene
Hypogonadotrophic hypogonadism - no or low FSH production
ARTs
Intrauterine insemination treatment
In-vitro fertilisation
Controlled ovarian hyperstimulation
Controlled ovarian hyperstimulation
The use of fertility medications to induce ovulation by multiple ovarian follicles
IVF
Egg collection - may be frozen
Intra-cytoplasmic sperm injection - helpful for men with low sperm count
Embryo development - implanted into endometrium after day 5
IVF live birth rate
national average 30-35% in under 35s
IVF live birth rate
national average 30-35% in under 35s
Function of testes
Spermatozoa and hormones
Structure of seminiferous tubules
Surrounded by myoid cells and basement membrane
Within - sertoli cells and spermatogenic cells
Pituitary control
LH stimulates Leydig to produce androgens
FSH stimulates Sertoli cells for spermatogenesis and conversion of testosterone to DHT by 5-alpha reductase
Testosterone synthesis
From acetate and cholesterol in Leydig cells
4-10mg per day
Hypophysectomy
Removal of pituitary gland causing shrinking of testes and spermatogenesis to arrest
Areas of seminiferous tubules
Basal compartment for mitosis
Adluminal compartment meiosis
Mitosis
Prospermatogonia reactivated at puberty
A1 and B spermatogonia
Primary spermatocyte
A1 spermatogonia vs B spermatogonia
A1 spermatogonia replenish spermatogonia
B spermatogonia form mature sperm
Meiosis
Meiosis I: secondary spermatocytes formed (2 cells with 2 pairs of chromosomes)
Meiosis II: haploid spermatids (4 cells with 1 chromosome in each new cell)
Spermiation
Release of spermatozoa into lumen of seminiferous tubules
Packaging
Tail for propulsion Mid-piece for mitochondrial energy Nucleus to package chromosomes Cap to aid sperm-oocyte fusion Acrosome to penetrate oocyte
Spermatogenesis
Mitosis
Meiosis
Packaging
Completed in 64 days
Residual body
Dustbin for unwanted cytoplasm during packaging
Eaten by sertoli cells
Final maturation of spermatozoa
Enter rete testis, pass through vasa efferentia and into epididymis
Physiological maturation of sperm between rete testis and epididymis to improve sperm motility - dependent on androgen stimulation
Spermatogenic wave
Multiple spermatogenic processes are occurring simultaneously in the same seminiferous tubule
Spermatogenic cycle
Time taken for appearance of the same stage within a given stage of the seminiferous tubule (16 days)
Semen formed by…
Seminal vesicle
Prostate
Bulbourethral gland
Cellular component of semen
Spermatogenic cells, spermatozoa, epithelial cells, leucocytes
Fluid component of semen
Fructose
Buffer for vaginal acidity
Sorbitol
Antioxidant e.g. VitC
Capacitation
Glycoproteins stripped from sperm surface as sperm travel through female reproductive tract to prepare the sperm for the acrosome reaction and fertilisation of egg
Causes hyperactive motility of sperm (from circular to whiplash movements)
What does the endocervix offer the sperm?
Thin, watery mucus to allow easy passage
Protection from vagina
Reservoir within endocervical crypts
Supplementation of energy requirements
Morphological variations of sperm
Head defects
Tail defects
Neck and midpiece defects
Normozoospermia
normal sperm values
Oligozoospermia
Low concentration
Asthenozoospermia
Too little motility
Teratozoospermia
Too many abnormals
Oligoasthenoteratozoospermia
Mixture of low concentration, too little motility and abnormal sperm
Azoospermia
No spermatozoa
Aspermia
no ejaculate
Biopsy of ST
Need to take 30 seminiferous tubules to fully understand the spermatogenesis