Week 2 RNU Lectures Flashcards
How common is infertility?
Roughly 1 in 7 heterosexual couples (can be as high as 1 in 3)
What is the definition of infertility?
1 year of unprotected vaginal intercourse in the absence of known causes of infertility in women of reproductive age
What is parity?
The number of times a woman has been pregnant
Under what age is the chance of a women conceiving better?
Under 35
What information is gathered in the history for ART/ infertility?
FEMALE
- female age
- parity
- date of last menstrual period + info on periods
- date and result of last smear
- past/ personal and family history - anything that points to infertility?
What information is gathered in the history for ART/ infertility?
MALE
- Age
- Occupation
- Children from any previous relationships
- Injuries (to genital region)
What lifestyle factors are gathered from both sexes?
- Smoking
- Alcohol
- recreational drugs
- STIs
- Driving
- Toxins, radiation - any cancer treatment
- Tight garments
- Weight - severely under or overweight can cause issues
What is the triad of reproductive physiology?
Ovary
Uterine tube
Uterus
What are the different groups of an irregular menstrual cycle?
- Group 1 - amenorrhea - low gonadotrophin and oestrogen activity
- Group 2 - ovulation isn’t happening (e.g. PCOS) but hormones are normal – they can be suitable for menstruation induction
- Group 3 - oocyte donation is often only option as the ovaries have stopped producing eggs
What issues could there be with the uterine tube?
- Hydrosalpinx
• Chlamydia – can often go unnoticed
- Pelvic adhesions
- Pelvic inflammatory disease
• Infection
- Endometritis – inflammation/swellingwhat is hydrosalpinx?
the uterine tube fills with fluid near the ovary and the blocked tube becomes distended and gives it a sausage shape – often bilateral – can destroy the egg or block the eggs passage.
What tests are done to check the uterine tube?
- Initial test will be to check for tubal patency
• HyCoSy – (hysterosalpingography)
• HSG (Hysterosalpingogram)
• Laparoscopy and dye test
What tests do most clinics do after the group of menstrual irregularity has been determined?
- FSH/LH
- Oestradiol
- Testosterone / DHEA /Free androgen index
- 17-hydroxyprogesterone (CAH)
- Thyroid function tests
- Sex hormone binding globulin
- Antral follicle count
- Anti-Mullerian Hormone
What is anti-Mullerian hormone a good indicator of?
a good indicator of ovarian reserve
What is the movement of healthy sperm described as?
Progressive motility - swims forward/ in the right direction
What are the reference values for healthy sperm?
semen volume - 15ml
- Total sperm number (million per ejaculate) = 39
- sperm concentration (million per ml) = 15
- Progressive motility (%) = 32
- Sperm morphology (normal %) = 4
- Vitality (live sperm %) = 58
What is oligospermia?
low sperm count
What is azoospermia?
The semen doesn’t contain any sperm
What happens if male infertility is suspected?
- Clinical examination to look for blockage
- CF screening/Y chromosome deletion/ karyotyping
- FSH levels
- IVF with ICSI (if sperm are available)
- Surgical sperm retrieval from testes or epididymis to use in ICSI
What is ICSI?
intracytoplasmic sperm injection
What are ART techniques?
- IVF
- Selective salpingography
- clipping/ salpingectomy
- IUI
- IVF with ICSI
What is a selective salpingography?
proximal tubal blockage – blocks uterine tube that is unhealthy
What is IUI?
intra uterine insemination – sperm put into uterus and hopefully healthy eggs will be fertilised
What is IVF?
In vitro fertilisation
When is IUI appropriate?
- Under 35
- Have functioning uterine tubes
- Mild endometriosis
- Single women
- Same sex couples
How is IUI carried out?
- Sperm (partner or donor) is washed and prepared
- Introduced via a catheter into the uterus at the optimum time
- Pregnancy test after 2 weeks
What are the steps of IVF?
- Ovarian stimulation hormone therapy
- Egg pick up
- Sperm preparation
- Egg fertilisation
- Embryo development
- Embryo transfer
What is ovarian hyperstimulation?
Hormones can be used to cause more than one dominant oocyte to be produced
How is ovarian stimulation carried out?
- Predict the patient’s response (age, antral follicle count, FSH levels)
- Suppression of the natural cycle – essentially put woman into menopause
• GnRH agonist or GnRH antagonists - Gonadotrophin (FSH) injections added gradually to stimulate growth of smaller follicles
• Close monitoring of serum oestradiol levels and follicular growth by ultrasound
How is ICSI carried out?
When the sperm count is not high enough, a single sperm is injected into the egg rather that in IVF when the sperms are left to fertilise the eggs naturally. The sperm is put near the nucleus of the egg
What are the risks of IVF?
- Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of fertility treatment
• Mild, moderate and severe (1%) - Due to the administration of gonadotrophins
• Higher risk if women has PCOS, is under 30, multiple pregnancy - Can lead to an increased risk of pre-eclampsia
Where do the testes develop?
Beside the mesonephros as an intra-abdominal organ
Why must the testes descend?
Normal body temperature is harmful to spermatogenesis
What temperature do the testes require?
A temperature 2oC lower than normal body temperature
What anchors each testis at its upper pole?
A cranial suspensory ligament
What is each testis anchored to at its lower pole?
The gubernaculum
What are the cranial suspensory ligament and the gubernaculum derived from?
Urogenital mesentery
When do the testes arrive in the scrotum?
A few weeks before birth, sliding down the processus vaginalis
What is the processus vaginalis?
An extension of the peritoneal cavity accompanied by muscular and fascial layers of the body wall forming the inguinal canal
When does the abdominal phase of testicular formation take place?
Weeks 8-15
What makes up the walls of the inguinal canal?
Upper wall: 2 Muscles:
· internal oblique Muscle
· transverse abdominus Muscle
Anterior wall: 2 Aponeuroses:
· Aponeurosis of external oblique
· Aponeurosis of internal oblique
Lower wall: 2 Ligaments:
· inguinal Ligament
· lacunar Ligament
Posterior wall: 2Ts:
· Transversalis fascia
· conjoint Tendon
What condition is commonly found in the inguinal canal?
Hernias
What divides each testis into lobules?
The tunica albuginea
What forms the blood-testis barrier?
Sertoli cells
What do Leydig cells secrete?
Testosterone
What is the function of the spermatic cord?
Transmits important structures to and from the testis - vas deferens, arteries (testicular ductus and cremaster), pampiniform plexus of up to 12 veins, nerves (genital branch of the genitofemoral nerve), lymphatic vessels and the fibrous remnant of processus vaginalis
What is a varicocele?
basically big squidgy veins at the back of the testicle
What is orchitis?
caused by infection – big swollen testes
What is epididymitis?
swollen epididymis – infection – this can lead on to cause orchitis. (posterolateral border)
What is a hydrocele?
a collection of fluid around the testicle in the tunica vaginalis– it will make the testicle very difficult to feel. – this will transluminate to a red colour
What is cryptorchidism?
- Also known as ‘impalpable’ or ‘undescended’ testes
What are potential long term consequences of cryptorchidism?
Long term consequences on testicular function including spermatogenesis and a risk of testicular cancer
What does testicular dysgenesis syndrome include?
hypospadias, micropenis, reduced semen quality, testicular cancer
What are risk factors for cryptorchidism?
- Birthweight <2.5kg
- Small for gestational age
- Prematurity
- Maternal diabetes, including gestational diabetes
- Environmental factors may also play a role for the risk of cryptorchidism
- Placental insufficiency / decreased HCG secretion / low maternal oestrogen levels
What environmental factors may play a role for the risk of cryptorchidism?
Organochlorines, phthalate monoesters, smoking have been linked to adverse effects in infant reproductive development
What consequence do adult men with persistent bilateral cryptorchidism have?
Azoospermia
When in cryptorchidism is the risk for testicular cancer greatest?
Bilateral cryptorchidism where the testis is intra-abdominal
What is orchidopexy?
Surgery to move an undescended testicle to its proper place in the scrotum
What investigations are done during a case of cryptorchidism?
- Ultrasound
- CT/MRI
- Laparoscopy
- consider karyotype
- biochemical test
What is the treatment of cryptorchidism?
- Operative treatment in centre with expertise
- Laparoscopy for non-palpable testis
- One stage vs two stage
When should treatment for cryptorchidism be carried out?
Should be carried out at age 6-18 months
What should the follow up after treatment for cryptorchidism be?
Clinical examination 12 months post op / for bilateral cases follow up at puberty
What are the immediate complications following treatment for cryptorchidism?
Immediate complications are haematoma, pain, wound infection
What are the hormonal treatment options for cryptorchidism?
- hCG stimulation test
- LHRH test
- Overall efficacy of approx 20%
- Up to 25% re-ascend later on
- Age dependent (most harm at 1-3 years)
What are the side effects of hormonal treatment for cryptorchidism?
pain, penile growth, groin pain, behavioural problems, temporary inflammatory changes in the testes, reduced testicular volume in adulthood
What does the efficacy of hormonal treatment of cryptorchidism depend on?
Efficacy depends on initial position of testis
What is Hypospadias?
The most common congenital anomaly of the penis that results in the urethral meatus lying proximal to the normal site and on the ventral aspect of the penis, and in severe cases opens on to the scrotum
What causes hypospadias?
- Cause not always clear
- Hormonal fluctuations – testosterone, progesterone
- Advanced maternal age
- Assisted pregnancies – IVF
- Teratogenic drugs / endocrine disruptor chemicals
- Reduced sensitivity to androgens
- Genetic factors
What is the treatment for hypospadias?
- Surgery
- Advise against circumcision
- Hormonal treatment prior to surgery
- Multiple procedures, mucosal grafting
- Scarring, curvature, strictures, fistula may occur
What are the two functions of the testis?
- Secrete testosterone - essential for spermatogenesis
- produce (mature) sperm by the process of spermatogenesis
What is the testis surrounded by?
A tough capsule - the tunica vaginalis and tunica albuginea which protects the seminiferous tubules
How many lobules is the testis divided into?
200-300
What is contained in the lobules of the testis?
The seminiferous tubules
When is the lumen of the seminiferous tubules formed?
At puberty
What is spermatogenesis?
The process by which immature stem cells (spermatogonia) proliferate and differentiate into mature sperm
How many sperm are made per day?
100mil
How long does it take to make mature sperm?
64 days
What are the 2 compartments in the testis?
Tubules and interstitium
Where are Leydig cells found?
In the interstitium between cells
What cells are found in the interstitium between cells of the testis?
Leydig cells
What surrounds developing germ cells in the testis?
Sertoli cell cytoplasm
What does Sertoli cell cytoplasm surround in the testis?
Developing germ cells
What are the three cell types in spermatogenesis?
- Spermatogonia
- spermatocytes
- Spermatids
What are the three stages of spermatogenesis?
- Mitotic proliferation
- Meiotic division
- Differentiation
What happens during meiotic division?
The chromosome number is halved
Where are spermatogonia found?
The basal compartment of the tubule
Are spermatogonia diploid or haploid?
Diploid
What are the types of spermatogonia?
Type A - “Dark A” and “Pale A”
Type B
What do Dark A spermatogonia do?
They are the “reserve” spermatogonia that ensure the man doesn’t run out of spermatogonia
What do Pale A spermatogonia do?
Divide (by mitosis) to give Type B spermatogonia
What do type B spermatogonia do?
Divide to give primary spermatocytes
MITOSIS
What is the sequence of events that spermatocytes undergo during spermatogenesis?
- Primary spermatocytes enter Meiosis I –> this produces secondary spermatocytes
- secondary spermatocytes enter meiosis II –> this produces spermatids
What do spermatids differentiate into?
Mature sperm
What is spermiogenesis?
The differentiation of spermatids into mature sperm
What happens during spermiogenesis?
- No more cell division
- Change from Round to elongated
- Tail forms for motility
- Midpiece forms – lots of mitochondria
- Acrosome forms
- Cytoplasmic remodeling
- Nucleus compacts
What is found in the acrosome?
contains enzymes for fertilization
What happens to the residual body that is left behind from spermiogenesis?
It is phagocytosed by Sertoli cells
What is the residual body?
Excess cytoplasm that is left behind from spermiogenesis
What is the head of the spermatozoa?
- nucleas with compacted DNA
- Surrounded by the acrosome
What is the midpiece of the spermatozoa?
central filamentous core with mitochrondria that joins the head of the sperm to the tail
What is the function of the tail of the spermatozoa?
Flagellum to propel the sperm
What are Sertoli cells derived from?
The sex cords of the developing testis
What is the structure of Sertoli cells like?
Tall, simple columnar cells that span from the basement membrane to the lumen of the tubule
What is the function of Sertoli cells?
Surrounds germ cells forming pockets around them, providing nutrients, and phagocytosing excess spermatid cytoplasm.
Form the blood testis barrier
Produce Anti-Mullerian hormone
How are Sertoli cells connected?
tight junctions that seal the tubule into two compartments
What are the two compartments created by the tight junctions of the Sertoli cells?
- basal (close to the basal lamina)
- adluminal (towards the lumen) compartment.
What is the function of Leydig cells?
Make and secrete testosterone in response to LH from the pituitary
Why is the cytoplasm of Leydig cells pale?
They contain many cholesterol-lipid droplets
What does FSH stimulate the Sertoli cells to do?
Secrete androgen-binding protein into the lumen of the seminiferous tubules. Binding of testosterone in the lumen provides a local testosterone supply for the developing spermatogonia
What are peritubular myoid cells?
Squamous contractile cells that surround the basement membrane of the lumen of the seminiferous tubules
What is the function of peritubular myoid cells?
- Play a crucial role in the self-renewal and maintenance of the spermatogonial stem cell population - keep them alive and nourished
- Important in signalling to the Sertoli cells
What cells produce inhibin?
Sertoli cells
When do the Sertoli cells release inhibin into the blood supply?
When sperm count is too high - this inhibits the release of GnRH and FSH
What regulates spermatogenesis?
All controlled by the brain:
- GnRH stimulates release of LH and FSH
- Leydig cells in testis make testosterone
- Testosterone and FSH stimulate the Sertoli cells to support the developing germ cells
- Once spermatogenesis reaches sufficient levels, the Sertoli cells produce inhibin
What are endocrine disruptors?
Exogenous substances that disrupt normal endocrine function (can increase or decrease)
What are examples of endocrine disruptors?
- Natural hormones
- Natural chemicals produced by plants/ fungi
- Synthetically made pharmaceuticals
- man-made chemicals
What is an example of a synthetically produced pharmaceutical that acts as an endocrine disruptor?
- Contraceptive pill
- Treatments for hormone responsive cancers
How do endocrine disruptors work?
- Mimic hormone biological activity by binding to a receptor and activating it (agonist)
- Binds to receptor preventing the binding of a natural hormone (antagonist)
- Interferes with metabolic processes in the body
What issues can endocrine disruptors cause with reproduction?
Reduced fertility, menstrual problems, early puberty, brain / behaviour problems, cancers
What are Phthalates?
Man made chemicals used to soften PVC plastics
What happens if anabolic steroids are taken in large amounts?
- Affects negative feedback systems
- Testis atrophy
- Liver and kidney damage
What is diethylstilboestrol?
Synthetic oestrogen that was prescribed to around 5 million pregnant women to prevent miscarriage and promote foetal growth
Why was diethylstilboestrol banned?
It affected foetal development and cause vaginal cancer
