REPRODUCTIVE ENDOCRINOLOGY Flashcards
Define contraception
prevention of
pregnancy before foetal implantation.
discuss characteristics of Period (menstruation)
- starts from the age of 12 (range 8-15)
- The period usually lasts 4-8 days
- The blood lost is approximately 5-12 tablespoons (up to180 ml)
- The mensural cycle is counted from the 1st day of menstruation
- The cycle lasts for 28 days (range 23-35)
- Continues until menopause (approx. age 52)
what occurs during the follicular phase of the menstrual cycle
when follicles in the ovaries mature and end in ovulation
what occurs during the luteal phase of the menstrual cycle
thickening of endometrial lining to facilitate implantation
what is the HPG-axis
Hormonal regulation –
the Hypothalamic-pituitary-gonadal (HPG) axis
explain the events in HPG-axis in the Follicular phase
in the Hypothalamus Gonadotropin-releasing hormone (GnRH)is Released in a pulsating manner (Follicular phase: Faster pulses)which stimulates the Anterior pituitary gland to release Follicle-stimulating hormone (FSH) and Luteinising hormone (LH) causing grow multiple eggs grow at the same time primary egg matures the fastest and released inhibin and oestrogen from the Ovaries is released Oestradiol (oestrogen) After 2 days over a high threshold → LH surge(ovulation)
what does FSH do
causes the follicles to grow multiple eggs grow at the same time primary egg matures the fastest
what does LH do
causes the LH surge which is needed for egg to be released
is oestrogen only inhibitory
oestrogen can be both inhibitory and non inhibitory depending on the levels
discuss signs of ovulation
Higher progesterone levels after ovulation
causes body temperature to increase
* High oestrogen level causes cervical mucous
to change texture to be like “egg white”
* Clearer and stringy instead of thick
* Sperm can pass the mucous easier
explain the events in the HPG-axis – Luteal phase
- Upon ovulation Corpus luteum (aka “Yellow body”), a small cyst inside the ovary, will form and produce high levels of Progesterone, and moderate levels of oestradiol.
- Corpus luteum does also produce inhibin.
- The lower moderate level of oestradiol will inhibit GnRH release
- Progesterone will prepare the endometrium for implantation of a fertilised egg
discuss the menses Phases of the uterine cycle
Day one, the first day of the mensuration/period
* Occurs if fertilisation did not take place
* Degeneration and shedding of the endometrium
* Often accompanied by cramps caused by
prostaglandins
discuss the proliferative Phases of the uterine cycle
Secretion of oestrogen from the maturing follicles lead to the proliferation of cells in the endometrium → endometrium thickens
discuss the secretory uterine cycle
Stimulation of changes to the endometrium by progesterone making it receptive to
implantation of the blastocyst
* Increased blood flow
* Increased uterine secretion
* Decreased contractility in the uterine wall
discuss Hormone levels in pregnancy
- When the fertilised egg successfully starts implants in uterus wall trophoblast tissue (to
become placenta) releases hCG - Measurement of hCG in urine is the main method to confirm pregnancy
- Oestrogen and progesterone will gradually increase together
discuss the effectiveness of hormonal contraceptive
what is the Combined Oral Contraceptives
Pills that contain oestrogens & progesterone (Progestogens) and Maintain sustained levels of hormones
through the cycle
what condition does the Combined Oral Contraceptives mimic
pregnancy
discuss oestrogen the mechanism of action of the Combined Oral Contraceptives
Oestrogen cause the inhibition of
hypothalamus and the Anterior
Pituitary Gland causes
→ Inhibits LH and FSH secretion
→ No follicle growth
→ No ovulation
→ No corpus luteum formation
discuss progesterone mechanism of action in the Combined Oral Contraceptives
- Progesterone also inhibits the
Anterior Pituitary Gland
→ Thickening of cervical mucous
(harder for sperm to pass
through)
→ Endometrial change
discuss the efficacy of Combined Oral Contraceptives
High chance to work well if taken as intended
* 99% efficiency to prevent pregnancy
* Failure is usually caused by missed doses, drug
interactions (some antibiotics), diarrhoea & vomiting
discuss the Side effects associated with Combined Oral Contraceptives
- Increased risk of CVD (cardio vascular disease (thrombosis) due to oestrogen)
- Breast cancer
- Minor effects include nausea, weight gain, depression
discuss the health benefits associated with Combined Oral Contraceptives
- Decreased risk of ovarian and endometrial cancer
- Decreased incidence of pelvic inflammatory
disease and ovarian cysts.
what are Progesterone Only Contraceptives
Progesterone Only Contraceptives are made of
synthetic progesterone
* Mini pill – taken every day without breaks
what are the other forms of what are Progesterone Only Contraceptives
Depo-injections and contraceptive implants
* Depo-injections last 8-13 weeks
* Contraceptive implants last 3 years
* Slow release, higher dose
discuss the mechanism of action of the mini pill as a form of Progesterone Only Contraceptives
Low dose progesterone inhibits the
Anterior Pituitary Gland
→ Anterior Pituitary Gland still
responds to GnRH
→ Inhibits LH and FSH secretion
→ Ovulation can still happen
depending on the HPGsuppression
→ Thickening of cervical mucous
(harder for sperm to pass through)
→ Endometrial changes
discuss the mechanism of action of implants and injections as a form of Progesterone Only Contraceptives
Mechanism of action – high dose
* High dose progesterone inhibits the
Anterior Pituitary Gland and the
hypothalamus
→ Inhibits LH and FSH secretion
→ No follicle growth
→ No ovulation
→ No corpus luteum formation
→ Thickening of cervical mucous
(harder for sperm to pass through)
→ Endometrial changes
discuss the efficacy of Progesterone Only Contraceptives
High chance to work well if taken as intended
* 99% efficiency to prevent pregnancy
* Failure is usually caused by missed doses, drug
interactions (some antibiotics), diarrhoea & vomiting
* Needs to be taken at a similar time every day! Higher risk to fail if not being consistent
discuss the side effects associated with Progesterone Only Contraceptives
- Rare: acne, breast tenderness and breast
enlargement, mood changes, headaches, nausea - Loss of periods – or irregular periods – or constant
bleeding - Depo injections – can take a long time to restore
normal fertility after treatment stops
explain the use of the Morning after pill
- Emergency contraception used within 72 hrs after unprotected sex.
- High-dose progesterone, one single pill.
- The primary mechanism of action is to inhibit ovulation.
- Suppression of HPG-axis
- Inhibition of FSH and LH secretion
- About 0.6-2.6% of women who take the morning-after pill will become pregnant anyway
explain the use of RU486 (Mifepristone)
- Progesterone ANTAGONIST
- Licensed in the UK for termination of pregnancy NOT post-coital contraception.
- Mechanism of action depends on the stage of the cycle:
- Mid-cycle – disrupts ovulation
- Luteal phase – prevents implantation
- After implantation – loss of foetus
- Can also be used to induce labour
What is Infertility?
Infertility is a disease of the male or
female reproductive system defined by the
failure to achieve a pregnancy after 12
months or more of regular unprotected
sexual intercourse.
How common is infertility?
1 in 7 couples will experience
difficulties to conceive
* 8 in 10 couples will conceive naturally
within a year (female age matters
what is primary infertility
Never conceived a child in
the past and has difficulty
conceiving
what is secondary infertility
Has conceived a child/children in the past and has difficulty conceiving again
what causes infertility in women
- ~25% ovulatory failure, often with polycystic
ovary syndrome (70% PCOS) - Tubal infertility (blocked fallopian tubes, inability
of tubes to receive oocyte from ovary) - Uterine disorders (including Endometriosis,
affects 10% of women world-wide)
what causes infertility in men
Reduced sperm count or function
* ~10-15% Azoospermia = no sperm
* Obstructive – sperm can’t get out
* Non-obstructive – spermatogenesis
is disrupted (hormone imbalances)
* Unusual shapes (some is normal!)
Testicular failure
* Reduced sperm production
* Reduced testosterone
what are some of the Risk factors for infertility
- Age
- Inappropriate BMI
- Sexually transmitted infections
- Can be asymptomatic and go unnoticed
- Smoking (cigarettes and marijuana)
- Alcohol
- Workplace hazards or toxins, chemicals, heavy metal particles
Name Hormone treatments for anovulation
Anti-oestrogen therapy
* Gonadotrophin therapy
* GnRH therapy
name assisted conception methods
- Intrauterine Insemination (IUI)
- In vitro fertilisation (IVF)
- Intracytosolic sperm injection (ICSI)
what is Anti-oestrogen therapy
Clomiphene: First-line therapy, used to restore ovulation
* Requires intact HPG-axis to function
describe the mechanism of action of Anti-oestrogen therapy
Selective oestrogen receptor
modulator Contains two components: zuclomifene and enclomifene
* Both blocks and stimulates the oestrogen receptors
in the hypothalamus.
what are the effects of Anti-oestrogen therapy
Reduces the inhibiting effects of oestrogen on
GnRH release.
* Faster GnRH cycling
* More FSH release
* Causes follicle growth followed by ovulation
can Anti-oestrogen therapy be used in combination with anything else and how does it work
Can be used in combination with exogenous Human
chorionic gonadotropin (hCG) that functions very
similarly to LH to promote ovulation
how can hCG be used
Normally released when the foetus implants in the uterus wall
* Produced by trophoblast that will form the placenta
* hCG is an analogue to luteinizing hormone (LH)
* Normally, hCG stimulates corpus luteum to produce progesterone which maintains the pregnancy
* If there are mature follicles, an hCG-injection will trigger ovulation within 38-40h
what is Gonadotrophin therapy
Human Menopausal Gonadotrophin (hMG)
* Used when HPG-axis is non-functional
explain the molecular mechanism of Gonadotrophin therapy
Provides exogenous
FSH and LH
* Bypasses the hypothalamic-pituitary
regulation
what are the effects of Gonadotrophin therapy
Stimulates growth and ovulation
Can gonadotrophin therapy be used in combination with hCG a hormone that functions anything else
Can be used in combination with hCG, a hormone that functions very similarly to LH to promote
ovulation
what is gonadotrophin-releasing hormone (GnRH) therapy
GnRH: For when there is an absolute or relative deficiency of
endogenous GnRH
* Congenital or amenorrhoea
explain the molecular mechanism of gonadotrophin-releasing hormone (GnRH) therapy
Exogenous hormone to replace the
endogenous hormone that is in low levels of missing
describe the effects of gonadotrophin-releasing hormone (GnRH) therapy
Stimulates the Anterior Pituitary Gland
* Leads to FSH and LH release
* Causes follicle growth followed by ovulation
* Pulsative stimulation required – continuous stimulation is
inhibitor
what is required for gonadotrophin-releasing hormone (GnRH) therapy
Pulsative stimulation is required – continuous stimulation is
inhibitory
when is intrauterine insemination used
- When vaginal sex is not possible
- If one partner has HIV
- If the partners are in a same-sex relationship
when can intrauterine insemination be performed
In a natural cycle – right after ovulation (tracking)
* Or after stimulation of ovulation
describe the process of intrauterine insemination
Sperm from a partner or donor is “washed” in centrifugation steps to create concentration of healthy sperm. catheter is inserted and sperm is injected using syringe
how long does the Intrauterine Insemination process take
Quick procedure – about 10 minutes, minor discomfort
when can in vitro fertilisation be used
When women under the age of 43 have
been trying to become pregnant for 2
years
* When 6 cycles of IUI have been used and
it did not work
what is In vitro fertilisation
IVF is when an oocyte becomes fertilised in a laboratory petri dish and the sperm can freely swim to the egg in the dish
describe how the natural menstrual
cycle is suppressed In vitro fertilisation process(1)
- Controlling the start of the process
- Gonadotropin-releasing hormone inhibits the cycle
- Continuous = inhibition
- Pulsative = stimulation
- Inhibition of the LH surge – we don’t want the ovulation to happen
describe ovaries to mature oocytes is stimulated in In vitro fertilisation(2)
Exogenous gonadotrophin (FSH) stimulate
oocyte maturation
why is Monitoring with ultrasound important in IVF (3)
- Follow oestradiol levels
- Administration of hCG at the correct time
Describe the process of Collecting the oocytes in IVF (4)
- Usually scheduled 34-36 hours after hCG
injection - The female is sedated, and the ovaries are located using ultrasound
- Oocytes are aspirated from the follicles using a needle that is passed through the vaginal wall
- Procedure takes 15-20 minutes
- Multiple oocytes are collected (5-14)
describe the process of Fertilising the oocytes in IVF (5)
The “best” Oocytes and “washed” sperm is
combined in a petri-dish for a few days
* Embryo is cultured for about 3-5 days and the
cell division is monitored with camera
* Certain stages of development should
happen in certain time-frames for the
embryo to be high quality
Describe the processes of Embryo transfer in IVF (6)
When to transfer is debated, day 3 vs day 5
What is Intracytoplasmic Sperm Injection (ICSI)
when sperm is injected into the cytoplasm of the egg using a fine needle
When is Intracytoplasmic Sperm Injection (ICSI) used
- When the sperm donor has very low
sperm count - Sperm is abnormally shaped or can’t
move normally (poor motility) - If IVF is performed previously and very
few oocytes were fertilised - If sperm is of poor quality or has been
frozen because fertility was at threat
describe the processes of ICSI
s performed similarly to IVF but Step 5:
Fertilisation of oocytes looks different
Assisted conception and success rates
- Assisted conception success rate is
associated with female age - Fresh embryo transfer is more successful
than transfer of frozen embryos
