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Fertility Flashcards

1
Q

Normal fertility

A

85% of couples in the general population will conceive within 1 year

95% by 2 years

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2
Q

Lifestyle advice to optimise conception

A
  • Female age linked to success, to a lesser extent male age also
  • Recommend intercourse every 2-3 days to optimise chances
  • Minimise alcohol intake- women to 1-2 units once or twice a week, men to max 3-4 units per day
  • Stop smoking for both men and women
  • No evidence re caffeine
  • Aim for BMI <30,
  • Aim for BMI>19
  • Healthy diet
  • regular exercise
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3
Q

When to investigate infertility?

A

No conception after 1 year of unprotected vaginal sexual intercourse.

Offer an earlier referral for specialist consultation where:
• the woman is aged 36 years or over
• there is a known clinical cause of infertility (e.g. endometriosis, tubal disease, anovulation, male factor infertility).
• there is reason for PIGD

Criteria for publicly funded fertility treatment in NZ:
Age <39
BMI <32
Non-smoker and no illicit drugs
<2 children between both partners

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4
Q

Testing of ovarian reserve

A
  • total antral follicle count (≤4 low response; >16 for a high response)
  • AMH (≤5.4 pmol/l for a low response and ≥25.0 pmol/l for a high response)
  • FSH (≥8.9 IU/l for a low response; ≤4 IU/l for a high response)
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5
Q

What are the options for screening for tubal abnormalities?
What is there accuracy?

A
  • HSG - sensitivity 53%, false positive 50%
  • Hysterosalpingo-contrast- sonography (HyCoSy) - false positive <10% and sensitivity approaching lap and dye test BUT not widely available
  • Lap and dye (GOLD STANDARD)
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6
Q

Fertility advice when the male has HIV

A

If the man is HIV positive, the risk of HIV transmission to the female partner is negligible through unprotected sexual intercourse when all of the following criteria are met:

  • the man is compliant with highly active antiretroviral therapy (HAART)
  • the man has had a plasma viral load of less than 50 copies/ml for more than 6 months
  • there are no other infections present
  • unprotected intercourse is limited to the time of ovulation.

Advise couples that if all the criteria above are met, sperm washing may not further reduce the risk of infection and may reduce the likelihood of pregnancy.

For couples where the man is HIV positive and either he is not compliant with HAART or his plasma viral load is 50 copies/ml or greater, offer sperm washing.

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7
Q

Fertility advice if the man has Hep B/C

A

For partners of people with hepatitis B, offer vaccination before starting fertility treatment.

Do not offer sperm washing as part of fertility treatment for men with hepatitis B.

For couples where the man has hepatitis C, any decision about fertility management should be the result of discussions between the couple, a fertility
specialist and a hepatitis specialist.

Advise couples who want to conceive and where the man has hepatitis C that the risk of transmission through unprotected sexual intercourse is thought to be low.

Men with hepatitis C should discuss treatment options to eradicate the hepatitis C with their appropriate specialist before conception is considered.

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8
Q

Screening prior to IVF

A
  • Includes psychological screening and counselling
  • Assessment of fitness to parent
  • Obesity, smoking status
  • Endocrine assessment of woman - FSH, LH, AMH, Antral follicle count
  • Pelvic structural abnormality (tubal or uterine factors)
  • Test for Hep B/C, HIV
  • Offer Rubella vaccination to the woman if non-immune
  • Cervical screening up to date
  • STI screen
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9
Q

10 most common causes of male factor infertility

A
  1. Obesity (BMI>30)
  2. Smoking and addictive substances
  3. Radiation- some data suggesting mobile phone close to the scrotum can affect sperm quality or chemo/radiotherapy for cancer
  4. Nutrition- aim for food rich in Vitamin C/antioxidants
  5. Supplements and steroids
  6. High testicular temperature e.g. sitting for long periods of time
  7. Infections
  8. Genital injuries
  9. Varicocele
  10. Age (more so >40)

Other: Chromosoma abnormalities e,g, microdeletion on Y chromosome, obstruction e.g. CF

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10
Q

WHO classification of ovulatory disorders

A

Group I: hypothalamic pituitary failure (hypothalamic amenorrhoea or hypogonadotrophic
hypogonadism).

Group II: hypothalamic-pituitary-ovarian dysfunction (predominately polycystic ovary
syndrome).

Group III: ovarian failure.

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11
Q

Group 1 ovulation disorders - TREATMENT

A
  • increasing their body weight if they have a BMI of less than 19 and/or
  • moderating their exercise levels if they undertake high levels of exercise.

• Gonadotrophin ovulation induction
contain FSH and LH as typically both are reduced
- 95% success at ovulation induction

• Pulsatile GnRH (if hypothalamic cause)
GnRH pumps expensive and limited to few tertiary centres, but more physiological and avoids increased risk of multiple pregnancy and OHSS

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12
Q

First line treatment for Group 2 ovulation disorder

A

• If BMI of 30 or over to lose weight

1st line:
• Letrozole (ideally as most effective)
• clomifene citrate
• metformin
• clomiphene AND metformin

For women who are taking clomifene citrate, offer ultrasound monitoring during at least the first cycle of treatment to ensure that they are taking a dose that
minimises the risk of multiple pregnancy.

For women who are taking clomifene citrate, do not continue treatment for longer than 6 months.

Women prescribed metformin should be informed of the side effects associated with its use (such as nausea, vomiting and other gastrointestinal
disturbances).

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13
Q

Second line and third line treatment for Women with WHO Group II ovulation disorders who are known to be resistant to clomifene
citrate

A
  • Laparoscopic ovarian drilling or
  • gonadotrophin ovulation induction with recombinant or urinary derived FSH

Women with polycystic ovary syndrome who are being treated with gonadotrophins should not be offered treatment with gonadotrophin-releasing hormone agonist concomitantly because it does not improve pregnancy rates, and it is associated with an increased risk of ovarian hyperstimulation.

Third line = IVF

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14
Q

Women with hyperprolactinaemic amenorrhoea MANAGEMENT

A
  • referral to endocrinologist
  • dopamine receptor agonists
    • bromocriptine (significant SE - nausea, vertigo, headache, postural hypotension)
    • cabergoline and quinagolide (newer, longer acting, fewer SE)
    • once prolactin < 1000IU/L 80% women will resume ovulation
  • surgical resection for macro adenomas >1cm, if significant pressure effects
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15
Q

Monitoring ovulation induction during gonadotrophin
therapy

A

Inform women about the risk of multiple pregnancy and ovarian hyperstimulation before starting treatment.

Ovarian ultrasound monitoring to measure follicular size and number should be an integral part of gonadotrophin therapy to reduce the risk of multiple
pregnancy and ovarian hyperstimulation.

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16
Q

Surgical options for tubal occlusion

A

For women with mild tubal disease, tubal surgery may be more effective than no treatment. In centres where appropriate expertise is available it may be considered as a treatment option

For women with proximal tubal obstruction, selective salpingography plus tubal catheterisation, or hysteroscopic tubal cannulation, may be treatment options because these treatments improve the chance of pregnancy

Women with hydrosalpinges should be offered salpingectomy, preferably by laparoscopy, before IVF treatment because this improves the chance of a live
birth.

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17
Q

Ashermanns syndrome

A

hysteroscopic adhesiolysis because this is likely to restore menstruation and improve the chance of pregnancy.

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18
Q

Ovarian stimulation for unexplained infertility

A

Do not offer oral ovarian stimulation agents (such as clomifene citrate, anastrozole or letrozole) to women with unexplained infertility.

Inform women with unexplained infertility that clomifene citrate as a standalone treatment does not increase the chances of a pregnancy or a live birth.

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19
Q

Indications for intrauterine insemination

A

Consider unstimulated intrauterine insemination as a treatment option in the following groups as an alternative to vaginal sexual intercourse:

• people who are unable to, or would find it very difficult to, have vaginal intercourse because of a clinically diagnosed physical disability or psychosexual problem who are using partner or donor sperm

• people with conditions that require specific consideration in relation to methods of
conception (for example, after sperm washing where the man is HIV positive)

• people in same-sex relationships

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20
Q

Predictors for more successful IVF:

A

Age
BMI 19-30
Previous successful pregnancy
Success decreases with each unsuccessful IVF attempt
Lifestyle factors: obesity, smoking, caffeine

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21
Q

What constitutes once cycle of IVF

A

1 episode of ovarian stimulation and the transfer of any resultant fresh and frozen embryo(s).

22
Q

Controlled ovarian stimulation in IVF

A

Use ovarian stimulation as part of IVF treatment.

Use either urinary or recombinant gonadotrophins for ovarian stimulation as part of IVF treatment.

When using gonadotrophins for ovarian stimulation in IVF treatment:
• use an individualised starting dose of FSH based on factors that predict success, such as:
－ age
－ BMI
－ presence of polycystic ovaries
• ovarian reserve

Ultrasound monitoring for efficacy and safety throughout ovarian stimulation.

23
Q

Triggering ovulation in IVF

A

Offer women human chorionic gonadotrophin (urinary or recombinant) to trigger ovulation in IVF treatment.

Offer ultrasound monitoring of ovarian response as an integral part of the IVF treatment cycle

24
Q

Luteal phase support after IVF

A

Offer women progesterone for luteal phase support after IVF treatment.

Do not routinely offer women human chorionic gonadotrophin for luteal phase support after IVF treatment because of the increased likelihood of ovarian hyperstimulation syndrome.

Inform women undergoing IVF treatment that the evidence does not support continuing any form of treatment for luteal phase support beyond 8 weeks’
gestation.

25
Q

Indications for ICSI

A
  • severe deficits in semen quality
  • obstructive azoospermia
  • non-obstructive azoospermia.

In addition, treatment by ICSI should be considered for couples in whom a previous IVF treatment cycle has resulted in failed or very poor fertilisation

26
Q

Intracytoplasmic sperm injection versus IVF

A

ICSI improves fertilisation rates compared to
IVF alone, but once fertilisation is achieved the pregnancy rate is no better than with IVF.

Indicated when:

  • 2 previous failed IVF cycles
  • Male factor infertility - particularly if testicular/epididymis aspiration required, or immotile sperm or absence of acrosome
27
Q

Indications for donor insemination

A
  • obstructive azoospermia
  • non-obstructive azoospermia
  • severe deficits in semen quality in couples who do not wish to undergo ICSI.

considered in conditions such as:
• where there is a high risk of transmitting a genetic disorder to the offspring
• where there is a high risk of transmitting infectious disease to the offspring or woman
from the man
• severe rhesus isoimmunisation

28
Q

Indications for oocyte donation

A
  • premature ovarian failure
  • gonadal dysgenesis including Turner syndrome
  • bilateral oophorectomy
  • ovarian failure following chemotherapy or radiotherapy
  • certain cases of IVF treatment failure.

Oocyte donation should also be considered in certain cases where there is a high risk of transmitting a genetic disorder to the offspring

29
Q

Long term health consequences of ovulation induction or IVF

A

No evidence to suggest long term health outcomes although data lacking for long term result

There may be a small increased risk of borderline
ovarian tumours

30
Q

Incidence of infertility

A

1:7 / 15%

31
Q

Causes of infertility

A
  • unexplained infertility (no identified male or female cause) (25%)
  • ovulatory disorders (25%)
  • tubal damage (20%)
  • factors in the male causing infertility (30%)
  • uterine or peritoneal disorders (10%).

In about 40% of cases disorders are found in both the man and the woman. Uterine or endometrial
factors, gamete or embryo defects, and pelvic conditions such as endometriosis may also play a
role.

32
Q

Investigations for infertility

A
  • Semen analysis;
  • assessment of ovulation,
  • tubal damage
  • uterine abnormalities;
  • screening for infections such as Chlamydia and susceptibility to rubella.
33
Q

Definition of ovulation induction

A

the production of a single mature follicle

34
Q

Definition of controlled ovarian hyperstimulation

A

the production of multiple mature follicles

35
Q

Is ovarian stimulation appropriate in women with a BMI greater than 35?

A

BMI> 35 is a recognised risk factor in pregnancy and
delivery and should be regarded as a contraindication to assisted fertility unless there are exceptional circumstances.

Ovarian stimulation in these circumstances should be deferred until appropriate weight loss by appropriate measures (e.g. diet, exercise, bariatric surgery, etc.) has occurred. This is expected to improve general health, may restore normal ovulatory function and enhance pregnancy outcome.

36
Q

Summary of guideline on cross border reproductive care:

  • Guiding principles?
  • 3 Key recommendations (RANZCOG guideline)
A
  1. Health and safety
    a. the health and safety of all parties involved in CBRC is the paramount guiding principle;
    any interventions that compromise the health and safety of any party cannot be supported,
    including unacceptable risk of transmission of infectious disease or the creation of higher
    order multiple pregnancies which expose both mother and baby to increased risks.
  2. autonomy
    a. all parties must be provided with appropriate information and counselling to make an
    informed decision whether to proceed to CBRC.
  3. equity:
    a. similar protocols and fees are applied and that the same information, counselling and
    support is provided to all parties;
    b. mechanisms are in place to ensure equity of access to limited resources in the visited
    country to the detriment of the local population.

Recommendations:

  1. Individuals intending to access CBRC should have an informed discussion with a specialist in O&G, taking into account suitability for pregnancy and the welfare of the unborn child.
  2. Practitioners facilitating CBRC should be familiar with their local regulatory and legal obligations. Practitioners are at all times subject to local regulations, which vary between and within Australia and New Zealand. Medical practitioners should be aware that significant penalties may apply for facilitation of certain reproductive practices, such as commercial surrogacy.
  3. The care of patients who have accessed CBRC should not, on their return home to Australia or New Zealand, be subject to any restrictions or penalties
37
Q

Hyperprolactinaemia and infertility

  1. Presentation
  2. Causes
  3. how does hyperprolactinaemia cause infertility?
A

Presentation: galactorrhoea, headaches, visual field defects and a variety of menstrual cycle disturbances, including anovulatory cycles and amenorrhoea.

Causes:

  • Prolactin-secreting pituitary adenomas (microadenomas <10 mm and macroadenomas that are ≥10 mm)
  • Idiopathic
  • Hypothyroidism (Thyrotrophic releasing hormone TRH stimulates lactotrophs to secrete prolactin)
  • Drugs – include estrogens, metoclopramide, methyldopa, tricyclic antidepressants, other psychotropic drugs
  • Renal failure - increased secretion and decreased clearance by kidneys
  • Liver cirrhosis - impaired estrogen metabolism leads to oestrogen accumulation, driving increasing prolactin secretion. Decreased dopamine levels reduce negative feedback loop, allowing prolactin production without restraint.
  • Physiological causes: Pregnancy, Lactation, Sleep, Stress, Chest wall stimulation.
  1. Has negative feedback on hypothalamus and decreases GnRH and therefore decreases LH and FSH secretion required for ovulation
38
Q

Steps in IVF:

A
  1. Patient and partner evaluation
  2. Controlled ovarian stimulation
  3. Oocyte retrieval
  4. Embryonic development
  5. Embryo transfer
  6. Luteal support with progesterone
39
Q

Which genetic conditions should be looked for in primary ovarian insufficiency?

A

Fragile X premutation (50-200 trinucleotide repeats)

Turners sydrome (45XO, or 45 XO mosaicism with 45XX/45XY)

40
Q

When is IVF indicated for first line fertility treatment?

A

unexplained infertility,
tubal factor infertility,
severe male factor infertility
for PGD

41
Q

Alternatives to IVF?

A
  • Ovulation tracking
  • Luteal phase support
  • Ovulation induction
  • Gonadotrophin therapy
  • IUI
42
Q

Who is a good candidate for luteal phase support and what does it entail?

A

Suspect if:

  • luteal phase is less than 9 days
  • Hx of of premenstrual spotting

A progesterone less than 30pmol/ml seven days following LH surge supports this diagnosis.

Luteal phase support: PV progesterone (e.g. utrogestan) commenced 3-4 days post LH surge and
continued until placental progesterone production
is established at approximately 10 weeks gestation.

43
Q

Who is suitable for ovulation induction?

A

Women in both WHO group 1 and 2

  • Treatment with either oral medications (clomiphene citrate and letrozole) or injectable gonadotrophins.
  • The treatment cycle is monitored with serial serum hormonal monitoring and TVUSS.
  • This is combined with HCG to trigger ovulation and
    is followed by timed intercourse or intrauterine
    insemination (IUI).

Luteal phase support is offered, if required, and a pregnancy test is carried out 16 days following ovulation.

44
Q

How does clomiphene work?

What are the benefits and risks?

A

Selective oestrogen receptor antagonist (SERM). Has ER antagonist action of hypothalamus, increasing GnRH secretion and thus FSH secretion from anterior pituitary.

Administered for 5 days in the follicular phase, usually starting day 3 of cycle. Monitored for follicular response by serial USS for AFC or mid-luteal progesterone.

Typically continued for 3-6 months; if does not result in pregnancy consider other fertility Rx. Longer courses not recommended due to increased risk borderline ovarian tumours with prolonged use.

Cochrane OR 5.9 clomiphene vs placebo. Wide CIs so amount of effect uncertain.

Risks:

  • multiple pregnancy 5-7%
  • OHSS 1%
  • SE: headaches, visual disturbance, abdominal pain, irregular bleeding, vasomotor sx.
45
Q

Letrozole vs Clomiphene

A

Letrozole preferable to clomiphene due to:

Letrozole has also been demonstrated to have a 40-60% higher LBR (27.5% versus 19.1%) when compared with clomiphene treatment, particularly when used in women with PCOS.

Letrozole may also have a reduced rate of multiple pregnancies (twin rate 3–7% versus 7–10%), though this finding is not consistent between all systematic reviews.

46
Q

Letrozole

A

Oral aromatase inhibitor - inhibits the conversion of circulating androgens to oestrogens. This reduces negative oestrogenic feedback to the pituitary gland, resulting in the increased release of FSH and thereby promoting maturation of follicles.

administered in the follicular phase

47
Q

Gonadotrophin therapy

  • Who is it used for?
  • How does it work?
A

Used in:

  • women (or men) with hypogonadotrophic hypogonadism
  • second-line Rx for women with resistance to oral OI by letrozole, clomiphene +/- metformin

GT involves daily SC injection of recombinant FSH alone or in combination with recombinant LH (hypogonadotrophic hypogonadism).

GT will induce ovulation in 90% of patients and will achieve a fecundity of 25% in WHO group 1 (hypogonadotrophic hypogonadism) patients and 5–15% in WHO Group 2 patients (PCOS).

Risks:

  • multiple pregnancy (15%)- can be reduced by monitoring no of follicles
  • OHSS
48
Q

Intrauterine insemination

  • What does it involve?
  • Who is it good for?
A

Outpatient procedure which involves placing
laboratory-prepared sperm directly into the uterus
at the time of ovulation.

It delivers significantly larger quantities of high-quality sperm to the uterus than would otherwise be achieved via intercourse.

Used in:

  • donor cycles
  • when mechanical or social issues preclude intercourse.

IUI can be used as a stand-alone procedure or combined with ovarian stimulation.

Approximately 60% of couples will conceive after six cycles of IUI and the success rates are highest for the first three cycles and decline thereafter.

Risks of the procedure:
- Risks low, upper genital tract infection
an uncommon potential complication.
- When IUI is combined with ovulation stimulation there is an increased risk of both multiple pregnancy and OHSS.

49
Q

Risks of IVF

A

Acute complications:

  • OHSS (1/3 cycles, mod/severe in 3-8% cycles)
  • Cyst accident e.g. haemorrhage/torsion
  • Complications from egg retrieval - haemorrhage, infection/collection

Pregnancy complications:

  • GDM
  • Polyhydramnios/oligohydramnios
  • PTB
  • LBW/FGR
  • Abruption
  • Placenta praevia
  • Vasa praevia
  • Hypertensive disorders
  • PPH
  • VTE
  • Stillbirth

Long term:

  • No evidence for increased breast/uterine cancers
  • Possibly increased risk of borderline ovarian tumours in women who have FSH treatment

Men:
Men with abnormal sperm counts are at an increased risk of all cause mortality, poor sperm count is a sign of overall male health therefore fertility doctors should become comfortable assessing male health and not miss opportunities for lifestyle interventions

Children:

  • increased rates of congenital abnormalities
  • NCD risk increased
  • Multiple pregnancies risk
  • Increased risk of prematurity/LBW
  • Increased risk being born via CS
50
Q

How to reduce the risks of OHSS during IVF.

A
  • Pretreatment with metformin prior to ovulation induction, particularly in PCOS
  • Short protocol / GnRH antagonist for ovarian stimulation rather than long protocol / GnRH agonists (reduction by 40%)
  • Using GnRH agonist rather than HCG to trigger ovulation (reduction by 80%) or use lower dose HCG
  • Consideration of freezing embryos rather than fresh transfer if USS evidence of hyperstimulation or deemed high risk for OHSS

Fertility (10 decks)

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