Conception and subfertility Sarah Christie and Patrick Elder

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