O&G - Infertility Flashcards
1
Q
What is infertility?
A
Infertility is
the period of time people have been trying to conceive without success after which formal investigation is justified and possible treatment implemented
2
Q
When taking a Hx from pt with fertility issues what questions / factors are important?
A
- Age
- How long trying to concieve?
- Frequency of intercourse (every 2-3 days is optimal)
- Past pregnancies / births (with/without current partner)
- Contraception - when stopped? what type?
- Menstrual Hx - regularity, LMP?
- Smear Hx
- Galactorrhoea or hirsutism
- Systemic conditions e.g. diabetes, thyroid, IBD
- Excessive exercise or weight loss?
- Hx of STIs
- Hx of PID
- Hx of pelvic / tubal surgery
- PMH
- DH
- SH - occupation (pesticides, solvents), smoking, alcohol
3
Q
When should a woman be referred to a specialist for subfertility issues?
A
After at least 1-year of frequent UPSI (~ every 2-3 days)
4
Q
What issues might prompt you to to refer a woman with fertility issues soon than normal (e.g. > 1-year UPSI)?
A
Consider more prompt investigation / referral for subfertility if:
- Age > 35-yrs
- Known fetility issues
- Anovulatory cycles
- Severe endometriosis
- Previous PID
- Malignancy
5
Q
What % of couples will conceive after 1-year and 2-years of UPSI?
A
84% conceive after 1-year UPSI
92% conceive after 2-years UPSI
6
Q
Anovulation can be cause by primary ovarian failure or
secondary ovarian disorders - give some exmaples of each.
A
Primary Ovarian Failure:
- Premature ovarian failure (ovaries stop working < 40-yrs)
- Turner’s syndrome (45XO - hypogonadism)
- Autoimmune
- Iatrogenic e.g. surgery or chemo
Secondary Ovarian disorders:
- PCOS
- Excessive weight loss or exercise
- Hypopituitarism e.g. tumour, trauma, surgery
- Kallman’s syndrome (anosmia & hypogonadotrophic hypogonadism)
- Hyperprolactinaemia
7
Q
What is Primary Amenorrhoea?
A
Failure to start menses by age 16-yrs
8
Q
What are some causes of primary amenorrhoea?
A
Primary Amenorrhoea causes:
- Turner’s syndrome (45 XO)
- Testicular feminisation - when an XY individual becomes resistant to androgens due to abnormalities of X-chromosome –> female phenotype
- Congenital adrenal hyperplasia (caused by autosomal recessive disorders causing ↓ adrenal steroid –> ↑ ACTH –> ↑ adrenal androgens –> masculinization of female)
- Congenital malformations of the genital tract
9
Q
What are some causes of secondary amenorrhoea?
A
Secondary Amenorrhoea causes:
- Hypothalamic amenorrhoea (e.g. Stress, excessive exercise)
- Polycystic ovarian syndrome (PCOS)
- Hyperprolactinaemia e.g. prolactinoma (pituitary adenoma) - ↑ prolactin –> inhibits secretion of GnRH from hypothalamus –> ↓ FSH + LH
- Premature ovarian failure
- Thyroid disorder - either hyper or hypo
- Sheehan’s syndrome - hypopituitarism due to ischaemic necrosis due to blood loss during/after childbirth
- Asherman’s syndrome (intrauterine adhesions)
10
Q
What is premature ovarian failure, also called primary ovarian insufficiency?
A
When a woman’s ovaries stop functioning normally before she is 40
11
Q
What can cause premature ovarian failure (POF)?
A
Causes of POF:
- idiopathic (most common)
- chemotherapy
- radiation
- autoimmune
12
Q
What are the features of POF?
A
Features of POF:
-
Climacteric symptoms: hot flushes, night sweats
- Climacteric = period of life when fertility decline in women (i.e. menopause)
- Infertility
- 2ndary amenorrhoea
- ↑ FSH + LH
13
Q
How frequently should we advise pts trying to concieve to have UPSI?
A
UPSI every 2-3 days
14
Q
What advise should we give couples trying to conceive?
A
- UPSI every 2-3 days
-
< 1 or 2 units of alcohol once or twice per week
- Men - alcohol < 3-4 units per day and < 14/week
- Smoking cessation (mum & dad)
- Recreational drug cessation (mum & dad)
-
Weight loss - aim for BMI < 25 (men & women)
- Women BMI < 19 –> aim to gain weight
- Take folic acid - 0.4 mg (or 5mg if Hx of NTD, diabetes or epilepsy)
- Caffeine is fine
15
Q
How can we confirm that a woman is ovulating?
A
- Regular menstrual cycle - indicator that ovulation is occuring normally
-
Measure serum progesterone 7-days post-ovulation / 7-days prior to next expected period (not done if cycle is regular)
- Progesterone levels should peak 7-days after ovulation due to corpus luteum production - so if high then is evidence of ovulation ~ day 21 in cycle
16
Q
Measuring serum FSH, LH and Oestradiol can be used to determine where in the HPG axis a pathology can be causing fertility issues. For each of the following state whether FSH, LH and Oestradiol will be high or low or normal.
- Hypothalamic / pituitary dysfunction
- Ovarian pathology
- Premature ovarian failure
A
-
Hypothalamic / pituitary dysfunction (e.g. GnRH deficiency or excessive weight loss or exessive exercise, hyperprolactinaemia)
- FSH & LH & Oestradiol = low
-
Ovarian pathology e.g. PCOS:
- FSH = normal
- LH = ↑
- Oestradiol = normal
-
Premature ovarian failure:
- FSH = ↑
- LH = ↑
- Oestradiol = ↓
17
Q
What is the best marker for Ovarian Reserve testing?
A
AMH - anti-mullerian hormone
18
Q
What is Ovarian reserve?
A
It is the capacity of the ovary to provide egg cells capable of fertilization
19
Q
Where is AMH produced?
A
Immature, pre-antral and antral follicles
Antrum = fluid filled cavity of oocyte
20
Q
As part of serum progesterone analysis what should be done for the following measurements?
- < 16 nmol/l
- 16 - 30 nmol/l
- > 30 nmol/l
A
- < 16 nmol/l –> repeat, if consistently low then refer
- 16 - 30 nmol/l –> repeat
- > 30 nmol/l –> indicates ovulation
21
Q
What investigations might be done in cases of subfertility?
A
-
Semen analysis - all males!
- Abstinence for 2-5 days (not > 7) then sample (repeat in 3-months if abnormal)
- Serum progesterone (if cycle not regular) to confirm ovulation
- AMH - indicates ovarian reserve
- Prolactin - if woman has ovulatory disorder, galactorrhoea or pituitary tumour
- TFT - only if thyroid symptoms
- Hysterosalpingography (HSG) - if not hx of PID, ectopics or endometriosis –> reliable test to rule out tubal occlusion
- Transvaginal US - assess uterus + ovaries e.g. cysts, fibroids etc.
- HIV, Hep B and Hep C
- Rubella status - if woman is susceptible then vaccinate (do no conceive in < 1-month after vaccination)
- Chlamydia screen - if +ve give Abx and give Abx before uterine instrumentation if not screened
22
Q
What elements are analysed on semen analysis and what is considered normal?
A
Semen analysis:
- Semen volume: > 1.5 ml
- pH: > 7.2
- Sperm concentration: > 15 million per ml
- Total sperm no. > 39 million per ejaculate
- Total motility: > 40% motile or 32% or more with progressive motility
- Vitality: > 58% live spermatozoa
- Sperm morphology: > 4% with normal form
23
Q
Name 4 factors that influence spermatogenesis.
A
- Body-building drugs
- Smoking
- Male obesity
- Alcohol
24
Q
What is PCOS?
A
Polycystic ovarian syndrome:
- Commonest endocrine disorder in women
- Causes ~80% of anovulatory subfertility
- Cause not fully understood:
- Genetic elements
- Insulin resistance –> hyperinsulinaemia
- Hyperandrogenism (↑ ovarian androgen section)
- Obesity
25
What are the **Rotterdam** **Diagnostic** **criteria** for **PCOS**?
PCOS if **2 of the following** are present + exclusion of other disorders:
1. **Irregular** or **absent** **ovulations**
2. **Polycystic ovaries** - on pelvic US ≥ 12 antral follicles on one ovary, ovarian volume \> 10 ml
3. **Signs** of **hyperandrogenism**:
* Acne
* Hirutism
* Alopecia
26
What are the features of PCOS?
1. **Subfertility** / **infertility**
2. **Amenorrhoea** or **Oligomenorrhea** (infrequent periods)
3. **Hyperandrogenism**:
* Acne
* Hirsutism
* Alopecia
4. **Obesity**
5. **Acanthosis Nigricans** (due to hyperinsulinaemia due to insulin resistance)
27
What investigations might you do in suspected PCOS?
* **General examination**:
* ↑ BMI
* Hirsutism
* Acne
* Alopecia
* Acanthosis Nigricans
* **Impaired** **glucose tolerance test**
* **FSH**, **LH**, **prolactin**, **TFTs** and **testosterone**
* Hypersecretion of LH (~60% of cases) cause **↑ LH:FSH ratio** (not diagnostic)
* Prolactin - normal / slight ↑
* Testosterone - normal / slight ↑ (is ↑ significantly then consider other diagnosis)
* **Pelvic** **US** - looking for ↑ ovarian volume and ≥12 antral follicles on one ovary
28
What are some complications of PCOS?
* ↑ risk of **T2DM**
* ↑ risk of **gestational** **diabetes**
* **HTN** - more due to insulin resistance + obesity common in PCOS
* **Endometrial** b- infrequent or absent periods can cause endometrial hyperplasia (managed via progesterone based contraception)
29
How is PCOS managed?
* **Lifestyle** management:
* **Weight loss** - diet + exercise --\> can help with menstrual regularity + subfertility
* **Hirsutism** / **Acne**:
* **1st** line = **COCP**:
* ↓ serum androgens
* co-cyprindiol - provides antiandrogen effects + regular monthly bleed
* **2nd** line = topical **eflornithine** (anti-androgen)
* **3rd** line = **spironolactone** or **flutamide** or **finasteride**
* **Subfertility**:
* Ovulation induction with **Clomifene** (anti-oestrogen) or **gonadotrophins**
* Laproscopic ovarian diathermy - can trigger ovulation
* IVF
30
Do women with polycystic ovaries have PCOS?
NO!
PCOS is polycystic ovaries and symptoms!
31
What 3 investigations can be used for assesment of tubal patency?
1. **Hysterosalpingography** (**HSG**)
* Inject radio-opaque material into cervical canal, uterus and fallopian tubes visualised via fluroscopy (real-time x-rays)
* Easily done
2. **Laproscopy** + **Dye test**:
* 'Gold Standard' - dye pushed through uterus + fallopian tubes and enters abdominal cavity (rate of flow viewed via laproscopy - then suctioned)
* Done if pt has ↑ risk of adhesions or tubal pathologies e.g. due to past C-section or Hx of Chlamydia
* Pelvic pathology e.g. endometriosis / adhesions can be treated during
* Requires GA
* Surgical risks
3. **Hysterosalpingo-contrast-sonography** (**HyCoSy**):
* US + galactose-containing contrast medium (forced/pumped into fallopian tube so it can be seen on US)
* Similar sensitivity to HSG
* No radiation
32
What is Endometriosis?
**Endometriosis** = growth of **ectopic** **endometrial** **tissue**
**outside** the **uterine** **cavity**
* ~10% of women of reproductive age have some degree of endometriosis
33
What are the features of endometriosis?
1. **Chronic pelvic pain**
2. **Dysmenorrhoea** - pain often starts days before bleeding
3. **Deep** **dyspareunia** (pain on intercourse)
4. **Subfertility**
5. **Urinary** **symptoms** e.g. dysuria, urgency, haematuria
6. **Dyschezia** (painful bowel movements)
7. Blood in stool (less common)
8. Bimanual exam:
* Adnexal masses (endometriomas) or tenderness
* Posterior fornix nodules/tenderness
* Recto-vaginal nodules
9. May seen vaginal endometriotic lesions
34
How is endometriosis diagnosed / investigated?
**Laproscopy** (gold standard)
* Should not be performed in \< 3-months of hormonal management (leads to underdiagnosis)
* Laproscopy indicated by:
* NSAID-resistant lower abdo pain / dysmenorrhoea
* Pain + infertility investigation
* Pain resulting in days off school/work
35
How is Endometriosis managed?
Only manage if symptomatic!!
* **1st** line = **NSAIDs** +/- **Paracetamol** - if analgesia doesn't help ...
* **2nd** line = hormonal treatment **IUS** or **COCP** or **Progesterone**-**only** (e.g. pill, depo or implant)
* Can also use GnRH agonist --\> overstimulation of pituitary gland causes downregulation and thus de-sensitisation of pituitary to GnRH --\> ↓ FSH + LH --\> ↓ oestrogen --\> pseudomenopause (but can't be used in young women)
* 3rd line = **Laproscopic excision** / **laser treatment** - all lesions \> 3cm should be removed (rule out malignancy - rare)
* Last line is hysterectomy + bilateral salpingo-oophrectomy
36
What is ovarian hyperstimulation syndrome (OHSS)?
OHSS is a complication seen in some forms of **infertility treatment** e.g. **intracytoplasmic sperm** **injection** (ICSI) or **IVF** or rarely **Clomifene** therapy
* Proposed that presence of multiple luteinized cysts --\> high oestrogen + progesterone, but also **↑ vasoactive substances** e.g. VEGF
* Vasoactive substances --\> **↑ membrane permeability** --\> loss of fluid from intravascular compartment
Features:
* **Abdo pain** & **bloating**
* **Nausea** & **vomiting**
* **Ascites**
* **Oliguria** (↓ urine output)
* **Haematocrit** \> 45%
37
A 36 year old woman and her 38 year old partner present with primary female/ primary male/ primary couple subfertility. The woman’s periods are regular and she has no history to suggest a tubal factor. The semen analysis is normal.
What is the most appropriate plan?
* Clomiphene citrate 50mg days 2-6 of the cycle for 6 months
* Continue to try to conceive for a further 12 months and if unsuccessful, refer for IVF treatment
* Proceed to IVF treatment
* Stimulated IUI treatment (intrauterine insemination)
* Unstimulated IUI treatment
**Proceed to IVF treatment**
* Woman \> 36-yrs --\> proceed to IVF
* **IUI** or **clomiphene** do **NOT** **increase** the chance of conception in cases of **unexplained** **infertility**
