Fertility Flashcards
What are the 2 gonadotrophic hormones secreted by the pituitary gland?
FSH and LH
What does FSH do in males and females?
Males: testes to produce sperm via stimulation of sertoli cells
Females: growth of ovarian follicles and causes the ovary to secrete oestrogen
What is the role of LH in males and females?
Males: testes secrete testosterone via leydig cells
Females: ovulation and causes progesterone to be produced by the corpus luteum
How does testosterone act on the anterior pituitary and hypothalamus?
Negative feedback to reduce the production of LH and FSH
Negative feedback on hypothalamus to reduce the production of GnRH
How does oestrogen feedback?
Estrogen below 200 will exert a negative feedback
Oestrogen above 200 will exert a positive feedback of LH and FSH
What is GnRH?
Neuropeptide hormone synthesized and released from the GnHR neurones within the hypothalamus and is released in a pulsatile manner
Describe the relationship between GnRH pulses and release of FSH and LH
Oestrogen contractions above 200 will increase GnRH pulsatility driving the release of LH.
During the early menstrual cycle, GnRH frequency is spaced out so only FSH is released, once the frequency is quicker there will be subsequent release of LH
Explain GnRH during puberty?
Appropriate modulatio nof LH freuqncy is essential for puberty and reproductive function. The onset of pubertal maturation is associated with a steady acceleration in GnRH pusatility with a peak at night
What is considered delayed puberty?
In females, no period by 15
In males, no sign of testicular development by 14
Moderated by the activation of GnRH frequency
What are the 2 cycles of the menstrual cycle?
Follicular / proliferative phase
Luteal / secretory phase
What mediates the follicular phase?
FSH
What mediates the luteal phase?
Corpus luteum and therefore progesterone
What is day 1 of the menstrual cycle?
First day of menstrual bleeding
When is the LH surge and what does it do?
Day 14
Influences the follicle to produce progesterone
As progesterone increases it will shut off the production of LH
What is a follice?
An oocyte surrounded by follicular cells (granulosa and theca cells)
Growth of a follice is an increase in the number of follicular cells and the accumulation of follicular fluid
How does the endometrium change over the menstrual cycle?
Thickens under the influence of oestrogen and becomes a secretory tissue under the influence of progesterone
What receptors are found on theca and granulosa cells?
Theca cells: LH
Granulosa cells: FSH
What occurs in the granulosa and theca cells?
FSH acts on the enzyme aromatase to convert the androgen in oestrogen within the granulosa cell
Cholesterol is converted to androgen in the theca cell
How many oocytes are recruited within each menstrual cycle?
5/6
These will all grow but only the dominant follicle will be selected for ovulation. The dominant oocyte might be the one that is most vascular or has the most FSH receptors
How long after the LH surge does ovulation occur?
Approx. 34-36 hrs
How is the corpus luteum formed?
Following ovulation, release of an oocyte and follicle will convert into corpus luteum (full of cholesterol to produce progesterone).
Within the corpus luteum there are no granulosa and theca cells as under the influence of LH will transfer into luteal cells
What are the roles of oestrogen?
Increase thickness of vaginal wall
Regulate LH surge
Reduce vaginal pH through increase in lactic acid production
Decrease viscosity of cervical mucus to facilitate sperm production
What are the roles of progesterone?
Pro-gestational hormone to maintain pregnancy
Maintains thickness of endometrium
Responsible for infertile thick mucus to prevent sperm transport and help prevent infection
Relax the myometrium
Progesterone withdrawal regulates partition
How is sperm made?
Occurs within the testes
Under control of LH, FSH and testosterone
Entire spermatogenic process takes 70 days
Humans produce 1000 sperm every heart beat
What regulates the gate of sertoli cells?
Tight junctions
What receptors are found on sertoli cells?
FSH receptors
Induce spermatogenesis
What receptors are found on leydig cells?
LH receptors
Causes the secretion of testosterone
What is the function of testosterone?
Maintains integrity of blood testes barrier
Release of sertoli cells
What is oligomenorrhea?
Cycles last more thana 35 days
What is amenorrhoea?
Primary - never had a period
Secondary - had periods which then stop
How is ovulation assessed?
Mid Luteal serum progesterone should be over 30 nmol/L
How is spermatogenesis assessed?
Diagnostic semen analysis - oligozoospermia (sperm count), asthenozoospermia (motility), teratozoospermia (morphology)
What is group 1 ovulatory disorder?
Hypothalamic pituitary failure: failure to produce GnRH which leads to lack of oestrogen and progesterone
What are the biochemical signs of hypogonadrotrophic hypogonadism?
Low levels of FSH and LH
Oestrogen deficiency - negative progesterone challenge test
Normal prolactin
Amenorrhoea
What can cause hypothalamic pituitary failure?
Stress Excessive exercise Anorexia Brain/ pituitary tumours Head trauma Kallmans syndrome Drugs (steroids, opioates)
How is group 1 anovulation managed?
Stabilise weight Hormone therapy Lifestyle modification Folic acid 400 mcg daily Check prescribed drugs Rubella immune Normal semen analysis Patent fallopian tube
What hormone is given in group 1 anovulation?
Pulsatily GnRH
Up to 90% ovulation rate
82% conception rate in 12 months
FSH and LH injections but has a high risk of multiple pregnancies
What is group 2 anovulatory disorder?
Hypothalamic pituitary dysfunction
What will hypothalamic pituitary dysfunction disorders show biochemically?
Normal gonadotropins/ excess LH
Normal oestrogen levels - progesterone challenge test
Oligo/amenorrhoea
What is the commonest cause of type 2 anovulatory disorder?
PCOS
What is the criteria for PCOS?
Oligo/amenorrhoea
USS appearance - 12 or more follicles, increased ovarian volume
Clinical or biochemical signs of hyperandrogenism (acne, hirsutism) - testosterone, sex hormone binding globulin (SHBG)
What does insulin do to the SHBG levels?
Increased free testosterone leads to hyperandrogenism
What symptoms and signs are associated with PCOS?
Subfertility: ovulation induction Oligo/amenorrhoea: risk of endometrial hyperplasia Hirsutism Obesity Acne/ alopecia
What is clomifene?
An ovulation induction drug that will cause the release of FSH and LH
What are the 3 different ways to induce ovulation in PCOS?
Clomifene citrate
Gonadotropin injections - recombinant FSH
Laparoscopic ovarian diathermy
What is the role of metformin in ovulation induction?
Improves insulin resistance, reduction in androgen production and increase in SHBG
Restoration of menstruation and ovulation
Does not help in weight loss
What are the risks of ovulation induction?
Ovarian hyperstimulation
Multiple pregnancies
Risk of ovarian cancer
What can severe ovarian hyperstimulation lead to?
Renal failure
PE
DIC
ARDS
What are the associated maternal complications with multiple pregnancies?
Hyperemesis Anaemia Hypertension/ pre-eclampsia Gestational diabetes (risk of intrauterine death and still birth) Mode of delivery Post natal depression
What are the risks to the foetus in multiple pregnancies?
Early and late miscarriage Low birth weight Prematurity Disability Stillbirth/ neonatal death TTTS
What is diaminotic dichrionic twins?
Separate sacs and separate pregnancies
What type of twins are at the highest risk of TTTS?
Monochorionic diamniotic
What is TTTS?
Twin twin transfusion syndrome
Unbalances in vascular communications within the placental bed:
Recipient develops polyhydramnios
Donor develops oliguria, oligohydramnios and growth restriction
How is twin-twin transfusion syndrome (TTTS) treated?
Laser division of placental vessels
Amnioreduction
Septostomy
What are the symptoms of hyperprolactinemia?
Amenorrhoea
Galactorrhea
Always examine visual field
What investigations should be done in suspicion of hyperprolactinemia?
Normal FSH/:H
Low oestrogen
Raised serum prolactin >1000 it/l on 2 or more occasions
How is hyperprolactinemia treated?
Dopamine agonist
Cabergoline twice weekly
What is type 3 anovulatory disorder?
Ovarian failure
What will ovarian failure show biochemically?
Raised FSH and LH
Low oestrogen
Amenorrhoea
Menopausal
What is classified as premature menopause?
Below 40
What can cause premature ovarian failure?
Turner syndrome XX gonadal agenesis Fragile X syndrome Autoimmune ovarian failure Bilateral oophrectomy Pelvis radio or chemotherapy
How is premature ovarian failure treated?
HRT
Egg/embryo donation
Ovary/egg/embryo cryopreservation prior to chemo/radiotherapy
What should be asked in a gynaecological history?
Details of menstrual cycle Amenorrhoea Hirsutism Acne Galactorrhea Headaches Prolcatin
What biochemical tests should be done in a gynaecological work up?
Mid luteal progesterone
Early follicular phase: serum FSH, LH and oestreogen. Serum testosterone/ SHG, prolactin, TSH
Progesterone challenge test
