Subfertility Flashcards
(46 cards)
1
Q
What is the definition of Infertility?
A
- Defined as inability to conceive after 12 months of regular unprotected intercourse. Can be primary or secondary
- Primary: someone who’s never conceiving a child in the past has difficulty conceiving
- Secondary: where someone who has had 1 or more pregnancies in past but having difficulty conceiving again
2
Q
What are causes of infertility?
A
- Male factor (30%)
- Unexplained (20%)
- Ovulation failure (20%) – PCOS, Weight-related, Ovarian failure, Hyperprolactinaemia
- Tubal damage (15%) – Pelvic inflammatory disease, Pelvic surgery, Tubal occlusion and adhesions, Endometrioses
- Other causes (15%) - uterine Factors
3
Q
What are typical factors in the history of a couple struggling with infertility?
A
Female
- Age
- Duration of fertility
- Type of infertility
- Menstrual cycle
- Tubal surgery/PID
- Menorrhagia/dysmenorrhea/pelvic pain
- Pelvic surgery
Male
- General health
- Alcohol/smoking
- Previous surgery (hernia)
- Previous infections
- Sexual dysfunction
4
Q
What features are involved in an examination for infertility?
A
- BMI
- Body hair distribution
- Galactorrhoea
- Secondary sexual characteristics
- Pelvic examination (structural abnormalities, fixed or tender uterus)
5
Q
What are the basic investigations for Infertility?
A
- Semen analysis
- Serum progesterone 7 days prior to expected next period. [Day 21 of 28]
- Interpretation of serum progestogen
- <16 nmol/l = Repeat, if consistently low refer to specialist
- 16 - 30 nmol/l = Repeat
- >30 nmol/l = Indicate Ovulation
- Interpretation of serum progestogen
- Follicular phase LH and FSH - day 2
- Rubella status
- Tests of tubal patency - hysterosalpingography, diagnostic laparoscopy and dye
- Cervical screening and chlamydia
6
Q
What additional investigations may be indicated in infertility investigations?
A
- Female
- Pelvic USS, Hysteroscopy, Prolactin level/TFTs, Testosterone/SHBG
- Specialist – HIV, HEP B and C
7
Q
What are some key counselling points regarding infertility?
A
- Folic acid
- Aim for BMI 20-25
- Smoking/Drinking advice
- Advise regular sexual intercourse every 2 to 3 days
8
Q
How is infertility managed?
A
- Anovulation: clomiphene citrate, Gonadotrophins/Pulsatile GnRH, Dopamine agonists for hyperprolactinaemia, Weight loss/weight gain, Egg donation
- Tubal disease: Surgery, IVF
- Intrauterine insemination
- Male Factor: IVF, intracytoplasmic sperm injection, donor sperm
9
Q
What is Oligomenorrhoea?
A
- Oligomenorrhea is an infrequent period.
- Cycle >35 days but less than 6 months in length
10
Q
What are causes of Oligomenorrhoea?
A
- Constitutional
- Anovulation
- Polycystic ovary syndrome
- Thyroid disease
- Prolactinoma
- Congenital adrenal hyperplasia
11
Q
What are types of Amenorrhoea?
A
- Primary Amenorrhoea: failure to start menses by the age of 16 years
- Secondary Amenorrhoea: cessation of established, regular menstruation that previously occurred for 6 months or longer (Exclusion of pregnancy)
12
Q
What are causes of Primary Amenorrhoea?
A
- Turner’s syndrome (gonadal dysgenesis)
- Testicular feminisation
- Congenital Adrenal Hyperplasia
- Congenital Malformation of the genital tract: Imperforate hymen/transverse septum, absent vagina
- Delayed puberty
- Mullerian agenesis
13
Q
What causes Asherman’s Syndrome?
A
- Asherman’s syndrome, or intrauterine adhesions, may occur following surgey ( dilation and curettage).
- This may prevent the endometrium responding to oestrogen as it normally would.
14
Q
What are initial investigations of Amenorrhoea?
A
- Exclude pregnancy with urinary or serum bHCG
- Gonadotrophins: low levels indicate a hypothalamic cause whereas raised levels suggest an ovarian problem (e.g. Premature ovarian failure)
- Prolactin
- Androgen levels: raised levels may be seen in PCOS
- Oestradiol
- Thyroid function tests
15
Q
What are physiological causes of Amenorrhoea?
A
- Prepubertal
- Pregnancy
- Menopause
16
Q
What are clincial features and management of Haematocolpos?
A
- Definition: Haematocolpos is a term given to a blood-filled dilated vagina due to menstrual blood in the setting of an anatomical obstruction, usually an imperforate hymen.
- Symptoms: Cyclical pain, No bleeding
- Examination: shows bluish membrane at introitus
- Management: Cruciate incision to drain blood
17
Q
What is Premature Ovarian Failure?
A
- Onset of menopausal symptoms and elevated gonadotrophin levels before age of 40 years. Occurs in around 1 in 100 women
18
Q
What are causes of Premature Ovarian Failure?
A
- Idiopathic - the most common cause
- Chemotherapy
- Autoimmune
- Radiation
19
Q
What are clinical signs and investigations of premature ovarian failure?
A
Symptoms/Signs
- Climacteric symptoms: hot flushes, night sweats
- Infertility
- Secondary amenorrhoea
Investigation
- Raised FSH levels
- Raised LH levels
20
Q
How does normal ovulation occur?
A
- Close functioning of a number of positive and negative feedback loops between hypothalamus, pituitary gland and ovaries.
- Early follicular phase requires an increase in GnRH pulse frequency which increases the release of FSH and LH, to allow for stimulation and development of multiple ovarian follicles, and usually only one of which will become the dominant ovulatory follicle in that menstrual cycle.
- In the mid-follicular phase, FSH gradually stimulates estradiol production, following which estradiol itself produces a negative feedback loop on the hypothalamus and pituitary gland to suppress FSH and LH concentrations.
- In the luteal phase, there is a unique switch from negative to positive feedback of estradiol, resulting in a surge of LH secretion and this leads to subsequent follicular rupture and ovulation.
21
Q
What are the categories of Ovulatory Disorders?
A
- Class 1 (hypogonadotropic hypogonadal anovulation): notably hypothalamic amenorrhoea (5-10% of women)
- Class 2 (normogonadotropic normoestrogenic anovulation): PCOS is 80% of cases
- Class 3 (hypergonadotropic hypoestrogenic anovulation): premature ovarian insufficiency (5-10% of cases). Any attempts at ovulation induction are typically unsuccessful and therefore usually require in-vitro fertilisation (IVF) with donor oocytes to conceive.
22
Q
What is the goal of ovulation induction?
A
Goal to induce mono-follicular development and subsequent ovulation as opposed to multi-follicular development, and this is to ultimately lead to a singleton pregnancy, which tends to be far lower risk and therefore preferable
23
Q
What are forms of Ovulation induction?
A
- Exercise and weight loss
- Letrozole
- Clomiphene Citrate
- Gonadotrophin therapy
24
Q
What is the role of Letrozole in Ovulation induction?
A
- 1st line medication for PCOS patients due to reduced risk of adverse effects on endometrial and cervical mucous compared to clomiphene citrate
- Mechanism of action: Aromatase inhibitor, reducing the negative feedback caused by oestrogens to the pituitary gland, therefore increasing FSH production and promoting follicular development
- Side effects: fatigue, dizziness
25
How does Letrozole compare with Clomiphene Citrate?
* Letrozole has a higher rate of mono-follicular develop compared with clomiphene which is goal in ovulation induction
* Clomiphene Citrate has a higher rate of live births than letrozole therapy due to most women responding to clomiphene treatment and ovulation.
26
What role does Clomiphene citrate play in Ovulation induction?
* **Mechanism of Action:** Selective oestrogen receptor modulators (SERMs) which acts primarily at the hypothalamus blocking negative feedback effect of oestrogens. This subsequently leads to increased GnRH pulse frequency and therefore FSH and LH production stimulating ovarian follicular development
* **Side effects:** Hot flushes (30%), abdominal distention and pain (5%), Nausea and vomiting (2%)
27
What is the role of Gonadotrophin Therapy in Ovulation Induction?
* **Mechanism of action:** Pulsatile IV GnRH therapy infusion leads to endogenous production of FSH and LH leading to subsequent follicular development
* Used mostly for women with class 1 ovulatory dysfunction
* Considered in women with PCOS after other treatment have failed usually after weight loss, letrozole and clomiphene trial. This is due to risk of multi-follicular development and subsequent multiple pregnancy is much higher as well as increase risk of OHSS
28
What is Ovarian hyperstimulation syndrome (OHSS)?
* Complication seen in some forms of infertility treatment can be life-threatening if not identified and managed promptly
* Rarely seen with clomifene therapy but more likely to be seen following gonadotropin or hCG treatment. Up to one third of women who are having IVF may experience a mild form of OHSS
29
What is the pathophysiology that results in OHSS?
* Presence of multiple luteinized cysts within the ovaries results in high levels of oestrogens, progesterone and vasoactive substances such as VEGF.
* This results in increased membrane permeability and loss of fluid from the intravascular compartment to extravascular space which can result in life threatening complications such as hypovolaemic shock, acute renal failure and venous or arterial thromboembolism
30
What are classifications of OHSS?
* **Mild:** Abdominal pain, Abdominal bloating
* **Moderate:** (Mild+) Nausea and vomiting, Ultrasound evidence of ascites
* **Severe:** (Moderate+) Clinical evidence of ascites, Oliguria, Haematocrit \>45%, Hypoproteinaemia
* **Critical:** (Severe+) Thromboembolism, Acute respiratory distress syndrome, Anuria, Tense ascites
31
What is the management of OHSS?
* Fluid and electrolyte replacement
* Anti-coagulation therapy
* Abdominal ascitic paracentesis
* Pregnancy termination to prevent further hormonal imbalances
32
What is Polycystic Ovarian Syndrome?
* Complex condition of ovarian dysfunction thought to affect between 5-20% of women of reproductive age.
* Heterogenous endocrine disorder with unknown aetiology and some familial clustering.
* Both hyperinsulinemia and high levels of LH seen in PCOS and appears to be some overlap with metabolic syndrome
33
What are differentials for PCOS?
* Simple obesity
* Premature ovarian failure
* Thyroid disease
* Hyperprolactinaemia
* Congential Adrenal Hyperplasia
* Androgen secreting tumours
* Cushing’s syndrome
34
What are investigations for PCOS?
* **Pelvic Ultrasound:** multiple cysts on ovaries. Must be 12 or more in one or both ovaries and/or increased ovarian volume \>10cm3
* **Sex hormone binding globulin**
* **Total testosterone**
* **Free androgen index:** typically raised
* **FSH, LH, Prolactin, TSH**: ↑LH:FSH ratio**,** ↑/=Prolactin, =/↑Testosterone
* **Check for impaired glucose intolerance**
35
What are clinical signs and symptoms of PCOS?
* **Subfertility and infertility**
* **Menstrual disturbances:** oligomenorrhea and amenorrhoea
* **Hyperandrogenism:** Hirsutism, Acne, obesity
* **Obesity**
* **Acanthosis nigricans** (due to insulin resistance)
36
How is a diagnosis for PCOS made?
**_Rotterdam Criteria_**
1. Clinical or biochemical signs of hyperandrogenism
2. Oligo-/amenorrhoea
3. Ultrasound features
37
How is PCOS managed?
**General**
* Weight reduction. COCP used if women require contraception which can help regular her cycle and induce monthly bleeds
* Offer screening for glucose intolerance and screen mental health
**Hirsutism and Acne**
* COCP may be used to help but may carry increase of VTE
* Topical eflornithine may be tried if no response to COCP
* Spironolactone, flutamide and finasteride may be used under specialist supervision
* Acne: topical retinoids and antibiotics
**Infertility**
* Should be supervised by specialist. Refer to fertility services
* Reduce BMI to \<30
* Start folic acid
* Baseline fertility assessment including semen analysis on partner
* Clomiphene could be most effective treatment and 1st line. Metformin can also be used either alone or combined with the clomiphene
* Gonadotrophins can be trialled as well
**Wants regular periods**
* COCP
* Cyclical progestogens
38
What are long term implications of PCOS?
* **Metabolic disorders** such as impaired glucose tolerance and type 2 diabetes
* **Cardiovascular disease**
* **Obstructive sleep apnoea**
* **Infertility**
* **Recurrent miscarriage**
* **Pregnancy complications:** pre-eclampsia and gestational diabetes
* **Endometrial cancer**
* **Psychological disorders** such as anxiety and depression
39
What are the classifications of Female Genital Mutilation?
* **Type 1:** Partial or total removal of the clitoris and/or the prepuce (clitoridectomy)
* **Type 2:** Partial or total removal of clitoris and labia minora, with or without excision of labia majora (excision)
* **Type 3:** Narrowing of vaginal orifice with creation of covering seal by cutting and appositioning the labia minora and/or labia majora with or without excision of the clitoris (infibulation)
* **Type 4:** All other harmful procedures to the female genitalia for non-medical purposes for example pricking, piercing, incision, scraping and cauterization
40
What is the definition of FGM?
Procedures involving partial or total removal external female genitalia or other injury to female genital organs for non-medical reasons
41
What is the law regarding FGM?
Genital Mutilation Act 2003 in England, Wales and Northern Ireland and the Prohibition of Female Genital Mutilation (Scotland) Act 2005 in Scotland. **Both Acts provide that:**
* FGM is illegal unless it is a surgical operation on a girl or woman irrespective of her age: (a) which is necessary for her physical or mental health; or (b) she is in any stage of labour, or has just given birth, for purposes connected with the labour or birth.
* It is illegal to arrange, or assist in arranging, for a UK national or UK resident to be taken overseas for the purpose of FGM.
* It is an offence for those with parental responsibility to fail to protect a girl from the risk of FGM.
* If FGM is confirmed in a girl under 18 years of age (either on examination or because the patient or parent says it has been done), reporting to the police is mandatory and this must be within 1 month of confirmation.
42
What are complications of FGM?
**Short-term**
* Traumatic bleeding
* Infection: wound infection, septicaemia, gangrene, tetanus, necrotising fasciitis
* Damage to adjacent organs and incomplete healing
**Long-term**
* Gynaecological: infection, scarring and keloid, menstrual difficulties, urinary symptoms, infertility
* Infection: chronic genital abscess, vaginal infection, hep B HIV
* Menstrual difficulties: painful and prolonged periods (haematocolpos)
* Urinary symtoms: urethral strictures, poor urinary flow, recurrent urinary infections
* Obstetric: prolonged labour, perineal trauma, postpartum haemorrhage, still birth, neonatal resuscitation
Psychological effects: depression, anxiety, PTSD
43
What has to be addressed in consultations regarding female genital mutilation?
* Explain law on FGM, documenting the discussion and referring her to information provided in the Health Passport
* Provide interpreter if required (not a family member).
* Offer referral for psychological assessment and treatment.
* Offer specialist referral as appropriate, e.g. sexual health, urology.
* Make a clinical assessment of FGM (symptoms, examination) and need for de-infibulation. If de-infibulation is indicated, offer before pregnancy – it can usually be performed on an outpatient basis.
* Record data in accordance with the HSCIC FGM Enhanced Dataset. These include age at FGM, country where FGM was performed, date of entry to UK (if applicable) and past history of de-infibulation and/or re-infibulation.
44
In what cases should FGM be reported?
* Report all known cases of FGM in under-18s to the police, either by calling 101 or through existing local routes. Reporting is mandatory to ensure it fits with our child protection and safeguarding duties.
45
What is the reference ranges for Semen analysis?
WHO reference range
* Total sperm count in ejaculate: 39–928 million
* Ejaculate volume: 1.5–7.6 mL
* Sperm concentration: 15–259 million per mL
* Total motility (progressive and non-progressive): 40–81 percent
* Progressive motility: 32–75 percent
* Sperm morphology: 4–48 percent
* pH \> 7.2
46
What causes Delayed puberty?
* Delayed puberty with short stature
* Turner’s syndrome, Prader-Willi syndrome, Noonan’s syndrome
* Delated puberty with normal stature
* PCOS, Androgen Insensitivity, Kallman’s syndrome, Klinefelter’s syndrome
