Fertility Flashcards
How does the endometrium change throughout the menstrual cycle?
Proliferative phase: under oestrogenic stimulation. Increases in thickness and changes from simple columnar to pseudostratified
Secretory phase: under progestogenic stimulation. Increase in glands and fluid. Development of pinopodes
What is the definition of delayed puberty? What are some causes?
No secondary sexual characteristics by 14 years.
Can be split into hypo and hypergonadotrophic causes.
Hypo: AN, Kallmans, tumours, chronic illness
Hyper: Fragile X syndrome, Turners, DSDs, iatrogenic
List several disorders of sexual development and their pathophysiology.
Turner syndrome: 45XO. Ovarian agenesis.
46 XY gonadal dysgenesis: no testes develop, so phenotypically female
46 XY DSD (aka CAIS- complete androgen insensitivity syndrome). No AR response to androgens –> no virilisation despite formed testes.
46XX DSD (aka CAH). Lack of cortisol forming enzyme eg. 21 hydroxylase –> increased testosterone and virilisation.
Define amenorrhoea (primary and secondary) and oligomenorrhoea
Amenorrhoea: primary no period by 16 years, or secondary no period for 6 months w/o pregnancy
Oligomenorrhoea: irregular periods. Either cycle length >35 days or less than 9 periods/year.
List some causes of amenorrhoea and oligomenorrhoea
Primary amenorrhoea: Turners, Fragile X, CAH, Kallmans, Mullerian anomalies
Secondary amenorrhoea/oligomenorrhoea:
-Hypothalamic: exercise, weight loss, stress, tumours
-Pituitary: prolactinoma, Sheehan’s, iatrogenic
-Ovarian: PCOS, POI
What is the management of PCOS?
- Conservative: diet and exercise, hair removal
- Medical: COCP/cyclical progesterone to regulate periods and improve hyperandrogenism. Metformin. Cyproterone acetate or spironolactone for hyperandrogenism. Clomiphene for fertility.
What are some causes of female subfertility? Male?
General factors: advanced age, smoking/alcohol/drugs, chronic illness, obesity
Ovulatory disorders: PCOS, hypothalamic/pituitary causes
Tubal problems: PID, endometriosis, surgery
Uterine: fibroids, polyps, scarring
Male: genetic (Klinefelters, CF), iatrogenic, infection (mumps, orchitis), smoking/alcohol/drugs, obesity.
You see a couple (30 year old F) in the GP clinic who have come because they haven’t gotten pregnant after a year of trying for a baby. After the history, what kind of investigations might you consider as first line?
Female:
- BMI
- Bloods: day 21 progesterone. Consider LH/FSH, oestrogen, testosterone and FAI, prolactin, TFTs
- NAAT for chlamydia
- TVUSS if needed
Male:
- BMI
- NAAT for chlamydia
- SFA
You see a couple (30 year old F) in the GP clinic who have come because they haven’t gotten pregnant after a year of trying for a baby. Your first line investigations come back as normal for both of them. What do you do now?
Refer to secondary care. This should be done if:
- After 1 year of trying for women with normal Hx/exam/Ix who are under 36 years
- Before 1 year if any abnormal features or the woman is 36+
You are have seen a couple in the GP clinic for trouble conceiving. The SFA has come back showing low sperm count. What should happen now?
You should order a repeat SFA, 3 months after the first. If this is abnormal, then the couple should be referred to secondary care for further investigations, such as:
- Bloods: LH/FSH, testosterone
- Karyotyping
- CF screen
What are the different treatments for subfertility?
Treatments for the cause of subfertility:
- Medical: clomiphene citrate, dopamine agonists
- Surgical: fibroid/polyp removal, tubal surgery, endometriosis ablation/excision, etc.
ART: ovulation induction with gonadotrophins, IUI, IVF (+/- ICSI), egg/sperm donation
When is IVF indicated? What are the basic principles (explain to a patient)?
Indicated if tubal disease, failure to respond to OI/IUI, egg donation, need for PIGD
You will need to administer injections of hormones every day for about two weeks, which we will teach you how to do (very easy and not painful). During this time you will come in every other day to have a scan and blood tests to monitor your eggs. Then, we will give you a ‘trigger’ injection of a different hormone and then collect the eggs about 36 hours later in an operation.
The eggs will be combined with the sperm in the lab to fertilise them. We will then implanted one or two of these embryos into your womb. You may be given more hormones to take after this.
You are in a GP clinic. A 29 year old lady comes in and says she wants to get pregnant. What do you want to know?
Anything in particular she wants to discuss? (eg. any difficulties with conceiving, wants info, etc)
General assessment:
- Timing: when would you like to get pregnant?
- Sexual intercourse: frequency, any difficulties, contraception use
- Periods: cycle length, regularity, LMP
- Obs history
- Smear history
- PMH, immunisations
- DHx, folic acid
- SHx: smoking, alcohol, drugs, occupation, relationship, diet + exercise
- FHx of inherited conditions (+ partner)
You are seeing a 27 year old lady in clinic who is having trouble getting pregnant. What do you want to know?
- Sex: how long have you been trying? How regularly are you having sex? Any difficulties with sex?
- Pregnancies: Have you ever been pregnant before? Does your partner have children? Any troubles getting pregnant before?
- Periods: LMP, cycle length and regularity, HMB, dysmenorrhoea
- Symptoms as relevant: IMB/PCB, abnormal discharge, dyspareunia, abdo pain, acne, hirsutism, galactorrhoea, vision changes, hot flushes, difficulties sleeping, libido, bladder/bowel problems, stress/diet/exercise/weight loss
- Obs Hx if relevant
- STIs, smear
- PMH including operations, DHx
- SHx: smoking, drugs, alcohol, occupation
- FHx
- Partner: well? Any medical problems? Any previous STIs? SHx?
What advice would you give a patient who is attempting to get pregnant?
Can split into intercourse and optimising health. Optimising health is beneficial both for increasing chances of conceiving and also for having a healthy pregnancy.
- Sex: regular, unprotected sex every 2-3 days throughout the cycle
- Lifestyle: healthy diet, exercise, stop smoking and drinking alcohol, reduce stress, sleep well
- Folic acid supplements
- Medical: if any chronic health conditions, see the GP/specialist to discuss how you can prepare for pregnancy eg. change medications, optimise treatment
A 33 year old woman sees you in gynae clinic because she is having trouble conceiving. Her and her partner have been trying for 7 months. The GP has referred her because she had PID 7 years ago and needed admission to hospital. What investigations would you consider doing for this woman?
- Want to determine if she is ovulating. If she isn’t, then this needs to be addressed first. eg. cycle history, day 21 progesterone
- Tubal patency testing: in this case, because there is a known history of PID, this patient should be offered laparoscopy + dye for Ix of tubal patency.
In cases where there is no history/RFs for tubal factor: consider hysterosalpingogram (HSG) with Xray or hysterosalpingo-contrast-syntography with USS
How does clomifene citrate work?
Anti-oestrogen
Works at the hypothalamus + pituitary to prevent negative feedback of oestrogen –> FSH +LH –> ovulation
What is the first line treatment for infertility in PCOS?
Second line?
First line:
- NICE recommends clomifene, metformin, or combination
- Weight loss should also be encouraged
Second line:
-Laparoscopic ovarian drilling or gonadotrophins (OI)
What is the treatment for women with unexplained infertility?
- 2 years of regular unprotected sex
- IVF
When is intrauterine insemination indicated?
- Same sex partners
- Use of donor sperm
- Not able to have sex eg. psychosexual dysfunction
NOT in unexplained infertility, endometriosis, male factor infertility
Who is eligible for IVF? What are they permitted to have?
-Eligible: women who have not conceived after 2 years of trying, or women who can only get pregnant by IVF
- Depends on the CCG as to how many cycles are provided
- Nationally, women under 40 should receive 3 cycles, women 40-42 should receive 1 cycle (if never had before and have good reserve)
- Cycles done privately are included in the 3 cycles funded by the NHS
What are the signs and symptoms of OHSS? Split into severity.
Mild:
- Abdominal pain and distension, N+V
- Increased ovarian size
Moderate: mild +
-Ascites
Severe:
- SOB +/- pleural effusion, pulmonary oedema, PE
- Hypotension
- VTE
- Electrolyte imbalance
- AKI
Define the menopause. What is the average age of the menopause in the UK?
Cessation of menstrual periods, diagnosed after 12 months of no bleeding.
51
What is the perimenopause? What is another name for this?
The time between the onset of ovarian dysfunction and the diagnosis of menopaise (1 year after periods stop). Also known as the climacteric.
Describe the hormonal changes during perimenopause.
As ovarian reserve decreases, there is less oestrogen and inhibin B produced.
This results in an increase in GnRH pulsatility, which increases FSH and LH levels.
Testosterone also declines with age, while progesterone can be unpredictable.
How is menopause diagnosed?
Usually a clinical diagnosis if the woman is >45. If younger, hormone levels (FSH and oestrogen) should be measured.
A 49 year old woman comes to see you in the GP clinic and says she is having difficulty with hot flushes. They are causing her to have poor sleep, which is impacting her work performance. What would you like to ask her about?
- Hot flushes: when did they start, how have they changed over time, any triggers (caffeine, alcohol, smoking), how much is she sleeping, taking anything to help with symptoms?
- Periods: LMP, regularity, length, bleeding, PMB
- Other menopausal symptoms: poor concentration and memory, mood, libido, vaginal dryness + dyspareunia, urinary symptoms
- PMH including gynae, clots, cancers, CVD. BMI, BP.
- DHx, allergies
- FHx: clots, cancers, osteoporosis, CVD
- SHx: impact on life. Smoking
A 52 year old woman comes to see you in the GP clinic because she has not had a period in 4 months. Prior to this, she says she was having irregular periods, with varying cycle length and bleeding pattern. What information and advice would you like to give her?
- Want to ask about menopause symptoms and effect on life to determine desire for HRT. Also relevant medical history if HRT is being considered
- Explain what menopause is, common symptoms and complications (hot flushes + night sweats, low mood, poor concentration + memory, aches + pains, vaginal dryness, sexual difficulties)
- Lifestyle changes to reduce symptoms and consequences (diet + exercise to maintain healthy weight + reduce heart disease + bone health
- Discuss options for treatment
- Discuss contraception
What are the contraception options for perimenopausal women? When should contraception be stopped?
- Barrier methods eg. condoms. For all women who are sexually active at risk of STIs
- Copper IUD: suitable from 40-menopause
- Mirena: suitable from 45-55
- Progestogen-only implant: suitable, no increased risk
- Depot injection: increasing risk, consider alternatives
- COCP/progestogen mini pill: suitable. COCP 1st line. Stop COCP at 50 years
Women can stop using contraception at 55 years, even if still bleeding. If at risk of STIs, still continue condom use.
What is premature ovarian insufficiency? How is it diagnosed?
Decline in ovarian function in women under the age of 40.
Symptoms or menopause/menstrual disturbance AND raised FSH on 2 occasions 4-6 weeks apart.
Name some causes of premature ovarian insufficiency
- Turner’s syndrome
- Fragile X syndrome
- Idiopathic
- Iatrogenic: radiation, chemotherapy, oophorectomy
- Immune-mediated
What is the management of POI?
Very important to give HRT until the age of the natural menopause
The forms of HRT available include the COCP (higher levels of hormones than normal HRT, may be preferred for younger women), oral or transdermal (patches or creams) HRT. HRT is not a contraceptive, and there is still a small risk of pregnancy in POI so this needs to be considered.
When should HRT be offered? What types of HRT are there and what are the advantages and disadvantages of each?
HRT should be offered to all women with POI, and any women who are having difficulty with symptoms of perimenopause.
Vaginal oestrogen creams: good for vaginal dryness and GU symptoms. Does not work for vasomotor/psych symptoms. Safe, no risk of clots/cancers.
Systemic HRT (oral or transdermal)
- Risks: clots, CVD (stroke), breast cancer
- Benefits: decrease menopausal symptoms, reduce osteoporosis during treatment
- Transdermal >oral: lower risk of clots and stroke
What are the preparations of oral HRT?
Cyclical or continuous.
- Cyclical: useful for women still having periods. Take oestrogen only tablets for the first half of the cycle, then progesterone + oestrogen for the 2nd half -> period. Also in 3 monthly forms if irregular periods.
- Continuous: for women with no periods. Taken every day
A 52 year old woman sees the GP because of vaginal dryness, low mood, and poor concentration. She says she does not feel like herself and would like to try HRT. She has not had a period for 1 year. There are no contraindications in her history to HRT. How would you counsel this patient?
- Confirm she has gone through menopause
- There are several ways we can help with her symptoms
- Options: vaginal oestrogen creams to help with dryness, systemic HRT
- HRT benefits: reduces symptoms, can reduce risk of osteoporosis while on treatment
- HRT risks: increased risk of breast cancer, blood clots, CVD if older aged (60s)
- It is normal to have some abnormal bleeding during the first 3 months of use. After this time, it is important to talk to your doctor quickly if you experience bleeding
What are the contraindications to prescribing HRT?
For any women with menopausal symptoms and contraindications to HRT, refer to gynae.
- Current or previous breast cancer or endometrial cancer
- Liver disease
- Thrombophilia
- Previous VTE
- Family history of VTE/cancer **caution, refer to haem?
