Subfertility Flashcards
(52 cards)
1
Q
What is subfertility?
A
The unwanted delay of 2 years in achieving conception despite regular unprotected sexual intercourse. Affects 15% of the population in the UK and as women embark on conceiving pregnancies later in life, the incidence of subfertility is increasing.
2
Q
What is the impact of age on conception?
A
Advancing female age negatively effects the changes of both natural and assisted conception. Most cases have relative subfertility which can be attributed to one or more factors in one or both partners whilst a small number have absolute infertility i.e. impossible to conceive.
3
Q
What hormones can cause irregular/absent periods?
A
- GnRH pulses (hypothalamus): not measure routinely in clinical practice
- FSH/LH (pituitary): low - hypothalamic/pituitary pathology; normal - disrupted folliculogenesis, but oocytes present (seen in PCOS); high - low number/absence of oocytes
- Oestradiol (ovary): produced by granulosa cells
- MH (Anti-Mullerian hormone) (ovary): produced by pre-antral and small antral follicles. Regarded as best measure of oocyte reserve (can be measured at any time of cycle)
4
Q
What are the causes of ovulatory dysfunction?
A
- Hypothalamic: FSH and LH low, oestradiol low, GnRH deficiency, weight loss etc
- Pituitary: FSH + LH low, oestradiol low, hyperprolactinaemia, other pituitary dysfunction etc.
- Ovarian: (PCOD - FSH normal, LH raised, oestradiol normal) (premature ovarian failure - FSH and LH high, oestradiol low)
5
Q
How do you test ovarian reserve?
A
- AMH: can be measured anytime in the cycle, little inter-cycle variability, best marker
- FSH: baseline day 2-5 (when oestradiol levels are low), normal: 4-7iu/l, >9 = reduced reserve
- AFC: antral follicle count, small follicles 2-5mm, measured at any time in cycle, estimates remaining egg reserve
6
Q
What is the Tanner Scale?
A
A scale of physical development in children, adolescents and adults. The scale defines physical measurements of development based on external primary and secondary sex characteristics, such as the size of the breasts, genitals, testicular volume and development of pubic hair.
7
Q
What do you want to know in a history of infertility?
A
- Initial consultation should include full history from both partners as well as clinical examination. Regular coital frequency of 2-3x weekly is usually recommended.
- Ovulation: is the woman ovulating? If anovulation, why?
- Ovarian reserve: good, satisfactory, poor diminished
- Tubes and transport: problem with the tubes?
- Sperm: are sperms present in ejaculate? If not present or reduced number, why?
8
Q
What factors affect fertility?
A
- Female age
- Female BMI (<20 or >30)
- Uterine function - endometrial problems, fibroids, polyps
- Duration of trying: couples who have a short duration of infertility are more likely to conceive both with/without treatment
- Lifestyle: obesity, smoking, excessive alcohol intake, drugs
- Medical history: ensure patient’s medical conditions optimised for pregnancy e.g. diabetic control
- Previous pregnancy
- Infertility consultation is important for pre-conception counselling
9
Q
What investigations for infertility do you do for females with a regular cycle?
A
- FSH, LH and oestradiol: assessment of ovarian reserve (early follicular phase - day 1-5 of cycle)
- Progesterone: confirm ovulation, although a regular cycle is a very good indicator even without confirmation from progesterone measurements - mid-luteal phase (adjust to cycle length - 7 days prior to expected menses)
10
Q
What investigations for infertility do you do for females with an irregular cycle or amenorrhoea?
A
- FSH, LH: assess pituitary function and possible indicator of PCOD (early follicular phase or any time in very prolonged cycles)
- Oestrogen: assess associated ovarian function (anytime)
- Prolactin, free testosterone: explore causes of oligo/amenorrhoea (anytime)
11
Q
What initial investigations do you do for infertility in all females?
A
- Rubella serology: check/offer immunisation
- AMH: good indicator of ovarian reserve
- Cervical smear: ensure no cervical pathology before pregnancy
- Transvaginal USS: assess uterus and ovaries
12
Q
What initial investigations do you do for infertility in all males?
A
Semen analysis x2 (abstinence 2-5 days) - if 1st sample abnormal, 2nd sample after 3 months, assess spermatogenesis
13
Q
What factors influence spermatogenesis?
A
- Body-building drugs
- Alcohol
- Male obesity
- Smoking
14
Q
What do progesterone levels mean?
A
- <16nmol/l - repeat, if consistently low, refer to specialist
- 16-30 nmol/l - repeat
- > 30nmol/l - indicates ovulation
15
Q
What is PCOS/D?
A
- Elevated LH
- Insulin resistance
- These lead to: ovarian growth, ovarian cyst formation, androgen production
16
Q
What are the features of PCOS?
A
- Signs of androgen excess: hirsutism (excess hair e.g. facial hair), acne
- Obesity
- Irregular menses/amenorrhoea - infertility
17
Q
What are the investigations for PCOS?
A
- Increased serum testosterone (ovaries make more testosterone)
- Increased LH, decreased FSH (ratio can be as high as 3:1)
- Other tests include prolactin and TSH
- Pelvic USS: visualise enlarged follicles in ovaries (usually >10 follicles per ovary, normal ovaries 2-10mm, in PCOS >10mm)
18
Q
What is the criteria for PCOS?
A
Must have at least 2/3:
- Irregular menses - oligo/anovulation
- Evidence of androgen excess - hyperandrogenism (hirsutism/male pattern alopecia, acne, raised testosterone)
- Polycystic ovaries (>10 follicles per ovary)
19
Q
What is the treatment for PCOS?
A
- If not wanting to get pregnancy, then can give OCP which suppresses androgens - decreases testosterone and LH levels
- Weight loss
- If women wants to get pregnant: metformin (increases insulin sensitivity), or clomiphene (binds to hypothalamic oestrogen receptors which stops oestradiol binding - prevents negative feedback inhibition of FSH secretion (infertility drug)
- If <3 periods a year then risk of endometrial cancer
20
Q
What is the main side effect of clomiphene?
A
Ovarian Hyperstimulation Syndrome (OHSS) - ovaries enlarge, severe GI symptoms, abdo swelling, dyspnoea, pleural effusions, decreased urination (OHSS typically caused by drugs used to treat infertility). Up to 1/3 of women doing IVF may get mild form of OHSS.
21
Q
How do you check the fallopian tubes?
A
To check the patency, you can do a laparoscopy and dye test, hysterosalpingogram (HSG) or Hysterocontrast Sonosalpingogram (HyCoSy). Laparoscopy and dye test would be preferred if the woman is at increased risk of adhesions and tubal pathologies e.g. from previous CS or STIs. Also any further treatment, like adhesiolysis can be done at the same time. HSG is when they infect the dye into the uterus - it travels through the fallopian tubes then with XR they visualise it.
22
Q
What is ICSI?
A
Single sperm cell is injected directly into the cytoplasm of an egg. Typically done if infertile but pathology has been ruled our or concentration of sperm is very low in semen analysis.
23
Q
What is the epidemiology of endometriosis?
A
- Affects 7-10% of women in reproductive age
- 38% of infertile women have endometriosis
- 71-87% with chronic pelvic pain have endometriosis
24
Q
What is endometriosis?
A
The presence of endometrial tissue anywhere outside the uterine cavity. Endometriosis can spread to various organs, causing adhesions to them/between them. So, you can get a fixed, retroverted uterus, tender/nodular uterosacral ligaments, visible nodules on cervix/vagina, palpable rectal nodules, enlarged/tender ovaries (can feel nodules on examination).
25
Where can endometriosis be found?
It can cause adhesions and scarring commonly in the round ligament, fallopian tubes, sigmoid colon and posterior cul-de-sac i.e. uterosacral ligaments and rectovaginal septum can also spread to the brain, lungs, kidneys, ureters etc. It is most commonly found in the ovaries and is bilateral. It can cause endometriomas which are ovarian cysts, also called 'chocolate cysts', as when cutting it out, it's black inside. More rarely, it can be found in abdominal scars and umbilicus.
26
How is endometriosis visualised operatively?
Operatively, endometriosis can be visualised as clear, white lesions; powder burn lesions or dark red/blue domes.
27
What are the symptoms of endometriosis?
- Dysmenorrhoea (pain often starts day before bleeding)
- Deep dyspareunia
- Chronic pelvic pain
- Less common symptoms include dyschezia (constipation, painful bowel movements) and haematochezia (blood in stools). Adhesions can irritate the rectum.
- Subfertility
- Endometriosis is present in 30-50% asymptomatic infertility patients
28
What are the examination signs of endometriosis?
- Can often be no signs on physical exam, due to endometrial lesions being very small - may feel uterosacral nodularity on bimanual exam
- Can show fixed, non-mobile uterus, thats retroflexed due to adhesions
- May feel ovarian endometriomas
29
How do you diagnose endometriosis on laparoscopy?
Gold standard - send sample for histology
- 2 or more: endometrial epithelium, endometrial glands, endometrial stroma +/- hemosiderin - laden macrophages
- Negative histology doesn't exclude, so biopsy not always necessary
- If ovarian endometriomas are >3cm - send for histology to rule out malignancy
- If it's a simple ovarian cyst and <3cm then rescan in 6 months to assess progress but if endometriosis related then it must be removed
- Can be seen as clear white lesions, powder burn lesions and dark red/blue domes (usually white)
30
What other investigations can be used for endometriosis?
- Transvaginal USS: can't identify peritoneal deposits but can diagnose/exclude ovarian endometriomas, can identify disease in the bladder
- MRI: can identify deep infiltrating and uterosacral disease, can exclude other causes of pain like adenomyosis
- USS and MRI have little role in the diagnosis so if patient has significant symptoms then go straight for laparoscopy for definitive diagnosis
31
What is the non-hormonal treatment of endometriosis?
NSAIDs and simple analgesia
32
What is the hormonal treatment of endometriosis?
- 1st line: COCP, give as a continuous dose, not as 21 days on + 7 days off (need to completely suppress the ovarian hormones)
- Progesterone therapy (oral, injection or implant) e.g. medroxyprogesterone acetate
- GnRH antagonist (induces menopause) - can't be used long-term on young patients due to side effects of low oestrogen - can give HRT to maintain bone mass
- Danazol: suppresses LH and FSH, has androgenic properties, so women may experience hirsutism, acne and irreversible deepening of voice
33
What are the options for IUD in endometriosis?
- Mirena (LNG-IUS) - 1st line for menorrhagia and endometriosis (new guidelines state this is 1st line, not COCP)
- LNG-IUS = levonorgestrel-releasing intrauterine system
34
What is the surgical treatment for endometriosis?
- Laparoscopic or ablation appear similarly effective in relieving pain
- Cystectomy (with excision of cyst wall) for endometriomas should be performed laparoscopically as a stage 1 procedure
- Hysterectomy with bilateral salpingo-oophorectomy - if woman's family is complete (good curative procedure) - post-operative HRT should be provided until natural menopause age (~50yrs), give combined continuous HRT, oestrogen only preparation increases risk of recurrence
35
What factors affect tubal function?
- Endometriosis
- Infection: chlamydia, gonorrhoea, PID
- Pelvic surgery
36
What is the advice given pre-conception?
- Manage all pre-existing conditions properly - ensure full immunisation hx
- BMI ideally between 19-30
- Stop smoking, rec drugs and alcohol
- Intercourse: at least every 2 days from approx 6 days prior to presumed day of ovulation until 2 days after - no need to restrict intercourse to these times
- Folic acid: 0.4mg daily reduces risk of NTDs
37
What is the HSG test for infertility?
- XR test to outline the internal shape of the uterus and show whether the fallopian tubes are blocked
- A thin tube is threaded through the vagina and cervix, a substance known as contrast material is injected into the uterus and a series of XR/fluoroscopy images the dye (appears white)
- The dye will show any abnormality in the shape of the uterus or blockages in the fallopian tubes
38
What factors improve fertility?
- Female age <30yrs
- Previously conceived
- <3yrs of infertility
- Unprotected intercourse around ovulation time
- Female BMI 20-30
- Non-smokers
- Limited alcohol use
- No rec drugs
39
What is the impact of age on fertility and pregnancy?
The fecudability of women age 35-39 yrs (chance of conceiving spontaneously) is half of that at age 19-26 yrs. As fertility declines with age, the risk of miscarriage and fetal chromosomal abnormalities such as Down's Syndrome increase. Due to socioeconomic changes in modern days, childbearing is delayed leading to marked reduction in couple's ability to achieve pregnancies. In addition, advancing female age is also associated with a similar worsening trend in the outcome of assisted conception treatment.
40
What are the causes of infertility?
For many couples, the cause is multifactorial.
- Ovulatory problems 20-30%
- Tubal 20-30%
- Male factor 25-40%
- Unexplained 10-20%
- Endometriosis 5-10%
- Other problems e.g. fibroids 4%
41
What are possible causes of unexplained subfertility?
1. Subtle abnormalities in oocyte or sperm function: if poor or failed fertilisation is encountered after IVF, it is wise to resort to ICSI in subsequent cycles.
2. Defective endometrial receptivity: this can cause unexplained subfertility or recurrent early pregnancy losses.
3. Subclinical endometriosis: this can affect tubal function, oocyte quality, sperm function, ferilisation, embryo quality, endometrial receptivity, implantation and placentation.
4. Nutritional factors: zinc and magnesium deficiencies in women can affect fertility. Zinc, selenium and Vit E supplementation oppose the oxidative stress, enhancing the sperm DNA repair which improves sperm quality.
5. Undiagnosed or untreated coealic disease
6. Immunological factors: anti-phospholipid, anti-nuclear, antithyroid, anti-sperm antibodies and NK cells have been suggested as causes
7. Poor ovarian reserve may give clinical picture similar to that of unexplained subfertility
42
How does weight help with fertility?
Reducing weight can encourage the establishment of regular ovulatory cycles and if not, will increase the chance of ovulation with clomiphene. It is also beneficial for the woman to reduce her weight before achieving a pregnancy to reduce risks in pregnancy.
43
What can be done if subfertility is caused by a problem with the sperm?
Currently there are no treatments which have been shown to increase the concentration of sperm. The only option at present, for couples to increase their chance of conception is to use the sperm produced within IVF/ICSI treatment. ICSI increases the chance of fertilisation of an oocyte when the sperm concentration is low.
44
What is Primary Ovarian Insufficiency?
Other names: Premature Ovarian Failure, Hypergonadotropic Hypogonadism
POI = loss of function of ovaries before age 40 (finished periods before 40yrs). Common triad for diagnosis is amenorrhoea, hypergonadotropism and hypoestrogenism (pituitary keeps releasing more FSH/LH to get ovaries to release oestrogen, but ovaries don't respond). If it has a genetic cause it may be called gonadal dysgenesis, but cause is usually idiopathic.
45
What will blood tests show for primary ovarian insufficiency?
- Shows low oestrogen (oestradiol on tests) and high levels of FSH - shows that ovaries aren't responding to circulating FSH by producing oestrogen and developing fertile eggs. Ovaries will likely appear shrivelled.
- Age of onset can be 11yrs old or even exist from birth. If a girl never begins menstruation, it is called primary ovarian failure (don't confuse with primary ovarian insufficiency/premature ovarian failure)
46
What is primary ovarian failure?
Failure to begin periods
47
What are the symptoms of primary ovarian insufficiency?
Usually severe form of menopausal symptoms:
- Hot flushes
- Low libido
- Amenorrhoea
- Mood swings
48
What is the management of primary ovarian insufficiency?
- 5-10% women still get pregnant naturally, IVF has shown to work
- HRT
49
What do you need to rule out in postmenopausal bleeding?
Endometrial cancer until proven otherwise
50
What is the definition of a heavy period?
- Cannot use tampons as blood leaks
| - Passing clots (need to ask size)
51
What could cause postcoital bleeding?
Cervical abnormality such as polyp, ectropion or cancer.
52
What is the management of endometrial hyperplasia?
- MDT discussion
- Hysterectomy and bilateral salpingoophrectomy (vaginal hysterectomy – cervix removed, subtotal abdominal hysterectomy – cervix could be left)
- Option to preserve fertility – high dose progesterone, mirena coil
