Session 6

Question 1

Describe the epididymal maturation of sperm.

Functions of seminal plasma

Answer 1

• On entry to epididymis, spermatozoa not capable of movement
• Once at the tail of the epididymis they are capable of movement and have the potential to fertilise
• Addition of secretory products to surface of sperm

Maturation:

Dependent on support of the epididymis by androgens

Semen consists of Spermatozoa and Seminal plasma

• Seminal plasma derived from accessory glands of the male reproductive tract
• Functions of seminal plasma:
• Transport medium • Nutrition • Buffering capacity • Potential role for prostaglandins in stimulating muscular activity in the female tract

Question 2

What are the contents of seminal plasma?

Answer 2

Seminal vesicles

• 60% of volume
• alkaline fluid (neutralizes the acid: male urethraand female reproductive tract)
• fructose, prostaglandins, clotting factors (particularly semenogelin)

Prostate gland

• 25% volume
• milky, slightly acidic fluid
• proteolytic enzymes (breakdown clotting proteins, re-liquefying semen in in 10-20 minutes ) • citric acid, acid phosphotase

Bulbourethral glands (Cowper’s glands)

• Very small volume
• alkaline fluid
• a mucous that lubricates the end of the penis and urethral lining.

Question 3

Normal site of fertilisation?

Answer 3

Fertilisation site is normally ampulla of uterine tube

Question 4

What are the phases of the human sexual response?

Answer 4

• Excitement phase - Psychogenic and / or somatogenic stimuli
• Plateau phase
• Orgasm phase
• Resolution phase - Return to haemodynamic norm followed by a refractory period in males

Question 5

Describe how an erection is stimulated

Answer 5

First step in male sexual response (excitement phase) is erection which requires stimulation which can be psychogenic and/or tactile (from sensory afferents of penis and perineum). That gives a spinal reflex and then the efferents are both somatic and autonomic efferents through the pelvic nerve (PNS) and the pudendal nerve (somatic). These lead to the hemodynamic changes which give men an erection

Question 6

What does an erection require from the penile anatomy?

Answer 6

• Oraganised by Tunica albuginea which surrounds the corpus spingiosum and corpus cavernosa. Relatively rigid.
• Erection requires:

Sinusoidal relaxation and arterial dilation in corpora cavernosa and corpora spongiosum allowing more blood in.

• Venous compression prevents blood leaving and that is achieved by the rigid albuginea.

Question 7

How does parasympathetic innervation aid in getting an erection?

Answer 7

Parasympathetic innervation

• Fibres in the lumbar and sacral spinal levels conduct through the pelvic nerve and pelvic plexus onwards to the penis through the cavernous nerve to corpora and vasculature

Question 8

Describe the neurophysiology of erection

Answer 8

Need inhibition of sympathetic arterial vasoconstrictor nerves and activation of PNS

• Activation of non-adrenergic, non-cholinergic, autonomic nerves to arteries, releasing Nitric Oxide (NO)
• Post-ganglionic fibres release ACh
• ACh bonds to M3 receptor on endothelial cells
• A rise in [Ca2+]i , activation of NOS and formation of NO
• NO diffuses into vascular smooth muscle and causes relaxation (vasodilation)
• NO also released directly from nerves

Question 9

What causes an erectile dysfunction?

Answer 9

• Psychological (descending inhibition of spinal reflexes) causing reduction in NO
• Tears in fibrous tissue of corpora cavernosa so cant retain blood
• Vascular (arterial and venous) e.g from diabetes
• Drugs

Sildenafil/Viagra slows the degradation of cAMP which in turn causes penile erectionas if not broken down , you can maintain nitric oxide presence fo longer.

Question 10

How is emission and ejaculation carried out in the male sexual response?

Answer 10

This phase is under sympathetic control

Emission • Movement of semen into prostatic urethra • Contraction of smooth muscle in prostate, vas deferens and seminal vesicles

Ejaculation (orgasm) • Expulsion of semen

Occurs through:

• Contraction of glands and ducts (smooth muscle)
• Bladder internal sphincter contracts - Preventing retrograde ejaculation
• Rhythmic striatal muscle contractions (pelvic floor, and perineal muscles ischiocavernosus, bulbospongiosus)

Question 11

Summarise the autonomic control of male sexual function

Answer 11

Erection

• Sympathetic - Inhibition (reduction of tone at arterioles)
• Parasympathetic • Active

Ejaculation

• Sympathetic • Active • Contraction of ducts

Question 12

What are the menstrual changes in the female tract?

Answer 12

• The character of cervical mucus changes over the course of the menstrual cycle
• Oestrogen makes mucus thin and stretchy facilitating the movement of motile gametes through the female genital tract
• Once ovulation has occured oestrogen and progesterone togeher make mucus thick and sticky forming a plug, prevents any further access to any more male gametes and if pregnancy occurs then allows a small amount of protection

Question 13

What’s the difference in site of deposition of sperm and site of fertilisation?

Answer 13

Deposited at external os of cervix but fertilisation most often occurs at ampulla of falopian tube

Question 14

What is capacitation?

Answer 14

• Further maturation of sperm in female reproductive tract (6-8 hours)
• Sperm cell membrane changes to allow fusion with oocyte cell surface
• Tail movement changes from beat to whip-like action
• Head now capable of undergoing the acrosome reaction

Question 15

When is the fertile window? How are the gametes transported?

Answer 15

• Spermatozoa 48 -72hr • Oocytes 6 – 24 hr (max)
• Fertile period: sperm deposition up to 3 days prior to ovulation or day of ovulation
• Gamete transport
• Oocyte: beating cilia & peristalsis of uterine tube
• Sperm: own propulsion by its flagellum

Question 16

Give an overview of the events in fertilisation

Answer 16

• Occurs normally in the ampulla of the uterine tubes
• Requires loss of sperm outer shell (acrosome)
• Penetration of ovum membrane, fusion of ova and sperm membrane. penetration facilitated by whip like motion of the spermatazoa.
• Eventual formation and fusion of pronuclei

Question 17

What is the role of the acrosome?

Answer 17

• Derived from golgi region of developing spermatid
• Contains enzymes - Necessary for fertilisation

Acrosome reaction

• Sperm pushes through corona radiata (follicular cells) • Binding of sperm surface receptor to glycoprotein on zona pellucida • Triggers acrosome reaction • Digestion of zona pellucida

Fertilisation

• One sperm penetrates leading to fusion of plasma membranes, causes wave of calcium signalling in oocyte which initiates cortical reaction (changes plasma membrane) which prevents polyspermy

Question 18

How is meiosis II resumed after fertilisation?

Answer 18

• Series of calcium waves are activated following fusion of oocyte and sperm membranes
• Resumption of meiosis II occurs
• Pronuclei move together
• Mitotic spindle forms leading to cleavage resulting in first mitotic division

Question 19

What is the morula?

Answer 19

Cleavage indicates successful fertilisation and leads to further cell division resulting in a morula. Morula - 16 cells contained in the zona pellucida.

• Each cell in the morula at this stage of development is TOTIPOTENT
• i.e. has the capacity to become any cell type

Question 20

How can laboratory techniques aid in fertilisation? How can this help with disease diagnosis?

Answer 20

• Oocytes are fertilised in vitro and allowed to divide to the 4- or 8- cell stage
• The morula is then transferred into the uterus

Pre-implantation Genetic Diagnosis (PGD) - a cell can be safely removed from the morula and tested for serious heritable conditions prior to transfer of the embryo into the mother

Question 21

How does the blastocyst hatch?

Answer 21

• First differentiation into inner and outer cell masses
• Formation of the blastocyst, blastocyst hatches from zona pellucida so no longer constrained - now free to enlarge
• can now interact with uterine surface to implant

Question 22

Describe implanation and its associated possible issues

Answer 22

• Outer cell mass (trophoblast) interacts with endometrium
• Endometrium controls degree of invasion - At this stage endometrium is well into secretory stage with glands and vessels within endometrium well developed due to presence of oestrogen and progesterone.
• Ectopic implantation - Implantation at sites other than endometrium lined uterine cavity
• Invasion not controlled
• Implantation in lower uterine segment can cause placenta praevia - placenta lies low in the uterus and partially or completely covers the cervix. can cause severe bleeding during pregnancy and delivery. If you have placenta previa, you might bleed throughout your pregnancy

Question 23

How common are STIs?

Answer 23

Most cases of STIs affect people in the ages of 15 to 24. Chlamydia most common STI . STIs are fairly common especially in the more affected age range.

Question 24

Risk factors for developing an STI?

Answer 24

“Risky sexual behaviours” ◦ Multiple sexual partners ◦ Not using barrier contraception ◦ Early age first intercourse ◦ Certain sexual practices e.g. anal sex more likely to get infection.

Other association:

◦ Low socio-economic status ◦ Race/ethnicity ◦ Lack of immunisation (Hep B, HPV through sexual contact)

Question 25

What infections can cause urethral dischrge in men?

Answer 25

Sexually transmitted infections that cause urethral discharge:

Chlamydia: Chlamydia trachomatis

The most common STI in the UK

◦ Obligate intracellular bacterium (lets itself be phagocytosed) ◦ Unique cell wall (gram negative but doesn’t follow the exact criteria of gram negative); inhibits phagolysosome fusion (virulence factor)
Typically asymptomatic in men

◦ Can cause testicular pain, dysuria

◦ May have discharge

Gonorrhoea: Neisseria gonorrhoeae

“Gonococcus” ◦ Gram negative ◦ Diplococci ◦ Unencapsulated, pilated (has projections that help it adhere to mucosal membranes)

90% of men are symptomatic so easier to detect (~50% of women)

Most common cause of male urethral discharge

Causes thick, yellow discharge +/dysuria
Can cause reactive arthritis (infection disseminates to cause painful joints)

Non sexually transmitted infections that cause male urethral discharge:

Non-gonococcal urethritis (NGU)

Inflammation of the urethra caused by anything other than gonorrhoea along with associated discharge

Can be sexually transmitted (common)

◦ Chlamydia trichomatis ◦ Mycoplasma genitalium ◦ Trichomonas vaginalis

Can be ‘pathogen negative’(cant find causative organism) (less common, older men)

Question 26

Investigations when there’s discharge in men?

Answer 26

Urine sample - use first portion of urine (first catch urine)

◦ Gonorrhoea: Microscopy & culture, nucleic acid amplification tests (NAATs)

◦ Chlamydia: NAATs (most sensitive & specific)

◦ Urethritis: NAATS

◦ Excludes UTI as a cause of dysuria

Urethral swab

◦ Gonorrhoea

Also look at general markers for infection so, temperature, FBC, C reactive protein etc

Question 27

What can cause vaginal discharge for women?

Answer 27

Could be physiological
Menstrual cycle - Progesterone in the secretory phase (post-ovulation) causes thicker cervical mucus so can casue discharge.
Features of this are: ◦ Cyclical ◦ No other associated symptoms ◦ Clear

Sexually transmitted infections
As per men: (More women are asymptomatic)

◦ N. gonorrhoeae

◦ C. trachomatis (Chlamydia)

Can cause neonal conjunctivitis during prgenancy or delivery

◦ May have discharge

◦ May have postcoital/ intermenstrual bleeding

◦ May have dyspareunia

Trichomoniasis: Trichomonas vaginalis

Protozoa (‘Flagellates’) ◦ Presence of flagella (mobility) ◦ Optimal growth ~ pH 6.0 ◦ Vaginal pH ~4.0 so increased alkalinity of vagina favours acquisition of disease.
Causes copious, yellow, odourous discharge

Can also cause non gonnacoccal urethritis in men

Treatment: Metronidazole

Non-sexually transmitted infections
Candidiasis: Candida sp. (albicans)

Yeast: normal vaginal flora

◦ Activated in immunocompromised states, diabetes

◦ Favours high oestrogen (can be associated with COCP)

VERY ITCHY! ◦ White discharge ◦ Typically non-offensive (odour)

Bacterial vaginosis

Gardnerella vaginalis

Lactobacilli is protective against infection and normal flora of vagina 95%

Altered flora (excessive washing) can cause bacterial proliferation

◦ Increased risk of contracting STIs
Offensive smelling, white discharge

Insert slide 24

Question 28

What investigations would we use for women with discharge?

Answer 28

If infection is suspected ask about other features of the discharge: Itchy, colour, sexual history and vaginal hygiene?

Can be asymtomatic so screening is important

Risk of pelvic inflammatory disease

Vaginal swabs

Chlamydia: Vulvo-vaginal swabs (VVS), endocervical

Gonorrhoea: VVS, endocervical

Trichomoniasis: High vaginal swab (HVS) (posterior fornix)

Bacterial Vaginosis: Gram staining, KOH test (add drops of potassium hydroxide and positive test will give “fishy smell”)

Candida: HVS; Microscopy > Culture

Urine dip not as effective for detecting STIs in women

Question 29

What can cause genital lesions in men and women?

Answer 29

Sexually transmitted infections:

Viral: Human Papillomavirus (HPV)

DNA virus (non-enveloped)

Can cause genital or cutaneous warts

Many, many different types!

◦ 6 and 11 cause 90% of genital infections ◦ 16 and 18 have the highest association with cervical cancer

Can do PCR to identify high risk types (biopsy/swab)

Vaccination exists: ◦ Gardasil (6, 11, 16, 18) ◦ Cervarix (just 16 & 18

Viral: Herpes simplex virus (HSV-1 & -2)

DNA virus (enveloped)

Lifelong infection - Initial then recurrent infection
Can be asymptomatic initially, or present with painful ulcers/blisters

◦ Can be accompanied by systemic symptoms
HSV-1: also associated with “cold sores”

HSV-2: more likely to become infected with HIV)

Both vertical and direct transmission

Check all areas ◦ Genitals ◦ Mouth ◦ Anus
Swabs: PCR / NAATs

Management: Antivirals e.g. aciclovir ◦ Cannot eradicate the infection ◦ Reduce the severity and duration of current episode ◦ Limited effect frequency/severity of repeated episodes

Bacterial: Syphilis (Treponema pallidum)

Spirochete - gram-negative, motile, spiral bacteria

More common in men aged 24-35 and homosexual men.

Transmission: ◦ Direct contact ◦ Vertical transmission
Not as common generally ◦ 40% co-infected with HIV

Primary syphilis ◦ Typically painless ulcer(s)
Secondary syphilis (25% of untreated primary cases) presents 4 – 10 weeks after initial infection. Can be multi-system. Can enter a latent phase

Identify using microscopy / PCR, Serology

Management: Penicillin-based antibiotics

Question 30

General management for reproductive tract infections

Answer 30

Sexually transmitted infections

Co-infections are common - Similar route of transmission
May be asymptomatic so consider screening for others
Consider presenting complaint so you can arrange ppropriate investigation & therapy

Bacterial: Can give multiple antibiotics
e.g. azithromycin & ceftriaxone for chlamidia and gonorrhoea.

Targets different organisms

One antibiotic can augment the effect of the other

Patient education

Barrier contraception and other ‘safe sex’ advice

Avoid sex until course of treatment is completed

For non-sexually transmitted infections:

Use appropriate therapy for the organism:

Candida - anti-fungals

BV - antibiotics e.g. metronidazole

Try and remove precipitating feature e.g control diabtes/immunocomprimised state.

Patient education

Advice when taking COCP and vaginal hygiene

Question 31

What is pelvic inflammatory disease?

Answer 31

Infection of the uterus, fallopian tubes, and ovaries

Typically because of ascending infection:

◦ Chlamydia trachomatis ◦ Neisseria gonorrhoeae ◦ Gardnerella sp. ◦ Others e.g. Mycoplasma genitalium
Often polymicrobial

Other sources of infection: ◦ Intrauterine contraceptives (more to come) ◦ Other uterine interventions

Presentation:

SYMPTOMS
Lower abdominal pain, Dyspareunia, Purulent discharge, Abnormal uterine bleeding ◦ e.g. intermenstrual or postcoital

SIGNS

Pyrexia (+/-), Pain on palpation of abdomen

◦ Examined using bimanual vaginal examination (pain felt during this examination indicates positive test.)

Evidence of discharge/cervicitis (speculum)

PID: Complications
Chronic pelvic pain, pelvic abscess (tubo-ovarian), can lead to subfertility due to adhesions from chronic inflammation ◦ Increased risk of ectopic pregnancy ◦ Reduced likelihood of successful fertilisation
Peritonitis due to further spread

Fitz-Hugh Curtis Syndrome (peri-hepatitis) from spread to capsule of liver. Rare.

PID: Management
Prevention > Cure

Anitibiotics ◦ Give if clinically suspected – don’t delay because of investigations

NB: Negative swabs do not exclude PID

◦ Broad spectrum ◦ IV in more severe cases
Analgesia

Offer screening to sexual partner(s) (genito urinary medicine)

In those who fail to respond to treatment, laparoscopy is essential to confirm the diagnosis or to make an alternative diagnosis.

Question 32

What are the normal values for semen analysis?

Answer 32

Volume of ejaculate: 2-6 ml

Viscosity: liquefaction in 1hr

pH: 7-8

Count: equal to or more than 20million/ml

Motility: equal to or more than 50%

Morphology: 60% normal

Question 33

What are the pain differentials for PID?

What are the differentials for abnormal uterine bleeding for PID?

Answer 33

Ectopic pregnancy, inflammatory bowel disease, constipation, cholecystitis, appendicitis, UTI, endometriosis, ovarian cysts

Intermenstrual bleeding, postcoital bleeding, cancer

(use in context with pain, fever and discharge)