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Conception and subfertilitySarah Christie and Patrick Elder
Point Shoot Score
Erection & Ejaculation
Parasympathetic Sympathetic Somatic
Erection Emission Ejaculation
R G Tunstall 2014
• Stimulus (physical or psychological)
• Parasympathetic dilation of arteries• Increased blood flow compresses
veins• Build-up of blood causes erection
• Sympathetic impulses• Urethra fills with semen
• Contraction of muscles at base of penis
• Pressure forces semen through urethra
Coitus is the act of sexual intercourse that results in the deposition of sperms in the vagina at the level of the cervix.
What is coitus?
11-14 days (you may be given different answers by different lectures)
What is the fertile window?
Excitement Plateau Orgasmic Resolution
Remember: EXPLORE
What are the four stages of coitus?
Stages of fertilisation
Ejaculation• Sperm emission
into the vagina
Sperm deposition• Deposited in
upper vagina• Enters cervix
Reservoirs• Sperm
supported by mucus components
• Form reservoir in cervical crypts
Entry into uterus• Sperm swim (or
are transported with the help of uterine contractions) into the uterus and tubes
• Relatively few sperm reach the site of fertilisation
Vasocongestion and engorgement of the clitoris (leading to erection), vagina, labia minora and nipples
Secretion of lubricating fluid by the greater vestibular (Bartholin’s) on either side of the vestibule and a fluid transudate from blood vessels in the vaginal wall.
Smooth muscle relaxation of the vagina causes dilation of the vagina
Which changes in the female facilitate coitus? 3
Alkalinity
Lowered viscosity
(note that the properties of the cervical mucus change outside the fertility window – it becomes thicker and more acidic)
Which properties of cervical mucus facilitate sperm survival and transport? 2
1.5-5 ml
How much ejaculate is produced with each emission?
Testicles and epididymes
Seminal vesicles
Prostate gland
Bulbourethral and urethral glands
What are the four structures that contribute to ejaculate?
What are the components? In what proportions?
Testicles and epididymes
5% Sperm, testosterone, L-carnitine (antioxidant affecting motility)
Seminal vesicles 46-80% Secretion rich in fructose (nutrient), proteins and semen clotting factors, interleukins, prostaglandin E
Prostate gland 13-33% Phosphate and bicarbonate buffers, prostate specific antigen (PSA), coagulase (ie liquefying), zinc, citric acid, spermine, spermidine, putrescine
Bulbourethral and urethral glands
2-5% Lubrication of male reproductive tract. Can include anti-sperm antibodies
While still in the ovary, the ovum is in the primary oocyte stage
At this point, it is paused in prophase I of meiosis
Ovulation and fertilisation
The primary oocyte develops under the stimulation of FSH.
Just before it is released from the ovarian follicle, the oocyte completes the first meiotic division.
It forms the secondary oocyte and a first polar body, which is expelled from the nucleus.
The first polar body degenerates
The secondary oocyte is now arrested in metaphase II. It is now a haploid cell with 23 unpaired chromosomes.
At this point the oocyte is released from the mature ovarian follicle and ovulation occurs.
Ovulation and fertilisation
Polar body
Oolemma
Ooplasm
Zona pellucida
In the ampulla of the fallopian tube
Where does fertilisation occur?
1. Motility: sperm need to be able to swim against the action of tubal cilia
2. Capacitation: usually occurs after ejaculation in the female reproductive tract. Involves changes to outer glycoprotein coat of sperm allowing greater binding between sperm and oocyte
3. Acrosome reaction: in order to penetrate the zona pellucida, head of sperm (acrosome) has to undergo reaction to produce more enzymes so that it can cut through the zona pellucida
What are the 3 features of sperm that are essential for fertilisation?
Remember:
Mental Capacity Act!
Essentials for fertilization
Post acrosomal region
Acrosome reaction
• Sperm binding causes final maturation of oocyte/release of second polar body
• Sperm entry/binding to oolemma causes calcium transients which: • Activate the oocyte for further
development• Release cortical granules avoiding
polyspermy
• Embryo development occurs
Fertilisation
What is infertility?
Usually defined as 1-2 years of attempting pregnancy without success
(84% of couples in general population conceive within 1 yr and 92% within 2 years if having regular sex and not using contraception)
What is the average age of first pregnancy? 31 years
What is the average age of menopause? 51 years
At what age does fertility decline? Declines significantly from ~37 years. Very low
from 40 years onwards.
The numbers
COITUS
Coitus e.g. male impotence Ovulation e.g. anovulation due to polycystic
ovarian syndrome Iatrogenic or idiopathic e.g. hysterectomy Tubal e.g. pelvic inflammatory disease (PID) Uterine anomalies e.g. bicornuate uterus Sperm e.g. azoospermia
How can you remember the different categories of infertility causes?
Causes of Female Infertility
MEDICAL DIAGNOSIS: Anovulation
Primary or secondary ovarian failure
Polycystic ovarian disease Tubal disease or
blockage Uterine anomaly
AGE
IVF DIAGNOSIS:•Anti-sperm antibodies•Egg anomaly (genetic, cytoplasmic, maturation…)•Fertilisation failure or abnormality•Abnormal embryo development•Implantation problem
HPG (Failure to ovulate)
Uterine tube problems
Uterine anomalies
Cervical problems
List four possible anatomical points in the female reproductive system where problems
may lead to infertility
Normally 1 egg ovulated per cycle Oligo ovulation or anovulation is common May be associated with polycystic ovaries (which are
common in the fertile population too) May be associated with endocrine anomalies e.g. high LH,
high androgens, insulin insensitivity Endocrine treatments include anti- or partial-oestrogens, or FSH NB: it is important to avoid overstimulation if attempting pregnancy by
intercourse
May be associated with being overweight
Ovulation
Passage of radio-opaque dye from uterine cavity; hysterosalpingography
How, in principle, might you test whether uterine tubes are patent?
Previous pelvic infection or previous history of ectopic pregnancy
What particular feature in a patient’s history might lead you to suspect that the uterine tubes could be
blocked?
Causes of Male Infertility
Impotence (Psychosexual, drug induced, paraplegia etc…)
No sperm in ejaculate (azoospermia) Primary or secondary testicular failure Obstructive (includes vasectomy, CBAVD..) Retrograde ejaculation (sperm ejaculated into bladder)
Not many sperm (oligozoospermia <15million/ml) Idiopathic or genetic or acquired
Poorly motile (asthenozoospermia <32% progressive)
Abnormal morphology (teratozoospermia <4% normal)
Non-viable (necrozoospermia)
Anti-sperm antibodies
Y chromosome microdeletions
Sperm don’t bind to or fertilise egg
15-200 million.ml-1 (text book figures may vary); in a semen analysis 39 million /ml suggested
What is the normal range of sperm count (millions/ml)?
Motility Morphology Liquefaction time WBC count (should not normally be present
in semen) Immunobeading (test for anti-sperm
antibody)
What other factors may be assessed in semen analysis? 5
Psychological Endocrine (e.g. diabetes) Neurological Alcohol
Name 4 causes of erectile dysfunction in young men
Male fertility treatment
1. Correct any hormonal imbalances/blockages/psychological problems where possible
2. Obtain the best possible sample from ejaculate 3. If too poor, obtain best possible sample from surgical retrieval4. If sperm available, apply treatments to female partner in order
of least invasiveness/appropriate to any female factor of infertility• Artificial insemination• Intrauterine insemination• IVF• ICSI
5. If no sperm available, or ICSI declined, consider donor sperm.
ICSI used in >50% of all IVF cycles
Intracytoplasmic sperm injection (ICSI)
Injection of one immobilised sperm into egg
Injected avoiding presumed position of oocyte spindle~10% of oocytes damaged
Fertilisation, embryo development and pregnancy rates similar to IVF with normal sperm. Some increased abnormality rate, likely due to parental factors.
Risks of fertility treatment
Failure (~70% per cycle) Over response of woman to
stimulation drugs (OHSS or multiple ovulation)
Multiple pregnancy Advanced maternal age Psychological Known risks of embryological processes (eg ICSI,
sex chromosomal disorders, inheritance of infertility, possibly imprinting disturbance)
Unknown risks of embryological processes