Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Anna and louise > Reproductive stuff > Flashcards

Reproductive stuff Flashcards

1
Q

Definition of infertility

  • primary, secondary
  • fecundibility
  • fecundity
A

Failure to achieve a clinical pregnancy after 12 months of regular UPSI

In women >35y, use 6 months

Infertility affects 15% of women of reproductive age

ART = IVF + IUI (not OI)
Primary infertility = no previous pregnancies regardless of outcome
Secondary infertility = previous pregnancy regardless of outcome

Fecundibility = probability that a cycle will result in a pregnancy
Fecundity = probability that a cycle will result in a live birth
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Normal fertility - chances

A

Couple of reproductive age has a fecundity of 20-25% per cycle
<36y
- ~85% of couples with conceive within 12 months
- 93% after 24 months

If >36y - only 50% pregnant by 12 months

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Male history and exam for infertility

A 
Pregnancies fathered
Sexual dysfunction
Varicocele
PMHx / PSHx
- Mumps orchitis, undescended testes, inguinal hernia surgery, testicular injury, STI
- Major head or pelvic trauma
- Chronic illnesses, infections
Meds, allergies
FHx
Occupational exposures
Smoking, spa baths, caffeine intake, anabolic steroids, testosterone

General - HR, BP, BMI
Gynaecomastia, hair distribution
Abdominal exam - masses, scars, exam of inguinal area
Reproductive (if semen analysis abnormal)
- Varicocele, testicular volume and consistency
- Palpation of vas deferens
PR - prostate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Investigations for infertility

A

Ovarian reserve testing

  • Measures to predict likely ovarian response to gonadotrophin stimulation in IVF
  • Doesn’t reflect fertility
  • AMH
  • Antral follicle count
Baseline hormonal profile
- Day 2-3 LH, FSH, estradiol
- Day 21 progesterone
Pelvic USS
Assessment of tubal factor
- HyCoSy
- HSG
- If high risk - diagnostic lap + dye studies

Preconception bloods
- serology
- blood group and antibiotic testing
Consider endocrine tests - TFTs, prolactin, PCOS bloods

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Causes of infertility

A

Combined - 40%

Male factors -30%

Ovulatory dysfunction - 25%

Tubal factors - 20%

Other (e.g. cervical factors, peritoneal factors, uterine abnormalities) - 10%

Unexplained -25%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Lifestyle modifications for infertility

A

Couples should avoid smoking, alcohol consumption, recreational drug use
Smoking:
- Women: likely reduces fertility
- Men: association with reduced semen quality
Target BMI 18.5-25
- Weight loss of 10kg in an anovulatory obese patient can restore ovulation in up to 90%
- Men - BMI >30 are likely to have reduced fertility
Folic acid and iodine
Limit caffeine intake to 1-2 cups of coffee - but no consistent evidence that caffeine is a/w fertility problems
Reduce stress
Ovulation tracking
Coital advice

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

No. of PID episodes and Incidence of tubal infertility

A

1 – > 12%
2 –> 23%
3 – > 54%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

TV USS for Ix of infertility

- pro and cons

A

Can include 3D USS

Readily available
Less uncomfortable

Tubes are not seen if normal
Doesn’t assess tubal patency
Operator dependent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Hysterosalpingogram (HSG) for Ix of infertility

- pro and cons

A

Contrast x-ray study

Non-invasive
Outpatient procedure
No need for GA
Relatively low cost

Oil based dye (Lipiodol) –> tubal flushing, but risk of anaphylaxis

Risk of procedure related PID
Pelvic radiation
Risk of allergy to contrast
Uncomfortable
No information on ovaries or peritubal pathology
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Hysterosalpingo-contrast-sonography (HyCoSy) for Ix of infertility
- pro and cons

A

Done under ultrasound guidance

90% concordance rate of tubal patency at laparoscopy
USS therefore no risk of radiation
Best at imaging uterine cavity
Good at imaging fibroids
Allows detailed gynaecological scanning
Non-invasive
False occlusion rate 10-15%
- Can get spasm of tube
False patency rate 3-5%
Risk of procedure related PID
Risk of allergy to contrast
Uncomfortable
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Tubal dye studies during laparoscopy for Ix of infertility

- pro and cons

A

Methylene blue dye is instilled through the cervix and uterus, and through the fallopian tubes and visualised laparoscopically

Gold standard
Allows full visualisation of both tubes and concomitant treatment of pathology

Invasive procedure
Surgical and GA risks
Cost
No information of uterine cavity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Impact of Hydrosalpinges in fertility

A

Several reports have described detrimental effect on IVF
Leakage of fluid into cavity may impede implantation by flushing embryos or disrupting endometrium
Fluid contains microorganisms, debris, toxins, cytokines, prostaglandins

Laparoscopic salpingectomy (uni or bilateral) can improve pregnancy rates from IVF
- IVF + bilateral salpingectomy - improves LBR (doubled)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Treatment options for tubal factor infertility

A

Surgery vs. IVF

LBR with 3-5 cycles is 72% vs. tubal surgery is 24%
Need to balance with risk of OHSS and cost and access to IVF

Surgery - Catheter or guide wire (canulation)
- risks of tubal perforation, infection, ectopic pregnancy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Management of unexplained infertility

A

25% of couples
Clomiphene or letrozole with IUI is superior to expectant management and natural cycle IUI for outcome of livebirth rate in couples with unexplained infertility
- Multiple gestation rate ranges from 0-12.5%

If >/=38y, then immediate IVF may be associated with higher pregnancy rate and shorter time to pregnancy
If <38y, consider 6 months expectant management or limited course (typically 3-4 cycles) of OS with IUI
- If unsuccessful, IVF is recommended

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Semen analysis instructions

A

One abnormal parameter on its own is not a predictor of infertility
Presence of multiple abnormalities has more clinical relevance
Recommended >2 samples are examined
2-5 day period of abstinence prior to producing sperm sample
Ensure sample collected and stored correctly - cool environment, to lab for processing within 1h

If abnormal, given lifestyle advice and retest in 3 months (Production of sperm takes ~3/12)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Lower reference range limits of sperm parameters

A

Semen volume - 1.5ml

Total sperm numbers - 39 million spermatozoa per ejaculate

Sperm concentrations - 15 million spermatozoa per ml

Total motility - 40%

Progressive motility - 32%

Sperm morphology - 4% normal forms

Vitality - 58%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Extended investigations if abnormal semen analysis

A

FSH, LH, testosterone (early morning)

  • low test, high FSH+LH –> karyotype
  • Hypogonadotropic hypogonadism - do prolactin
  • if all normal and azoospermia - evaluate for obstruction

TFT
Genetic tests
- Karyotype (Klinefelter - small firm testes)
- Y chromosome analysis for microdeletions
- CFTR gene mutation - if congenital bilateral absence of vas deferens
Urine sample post ejaculation - to assess for retrograde ejaculation

Ultrasound - scrotal and transrectal

  • Presence of testicles and appearance
  • Presence of vas deferens
  • Additional structures - mass, hydroceles, varicocele
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Causes of azoospermia (or oligo)

A

Pre-testicular (hypogonadotropic)

  • Androgen intake
  • Pituitary tumours (craniopharyngioma)
  • Head trauma, surgery, irradiation

Testicular (~60% of azoospermia cases)

  • Undescended testis
  • Torsion / Injury / trauma
  • Neoplasm / Post-chemotherapy
  • Klinefelter syndrome
  • Microdeletions of Y chromosome
  • Autoimmune- anti-sperm antibodies associated with vasectomy reversal
  • Drugs - anabolic steroids, marijuana, alcohol
  • Environmental exposures - to heat, radiation, chemicals

Obstruction

  • Infective - mumps
  • Post-vasectomy
  • CBAVD

Disorders of sexual function and / or ejaculation interfering with intromission

  • Retrograde ejaculation
  • Anejaculation, e.g. spinal injury
  • Drugs - anti-depressants, anti-hypertensives
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Reversible factors for poor semen analysis:

A 
Smoking
Alcohol
Heat
Solvents (painters, decorators)
Lead

Tight clothing / underwear

NICE: Association between elevated scrotal temperature and reduced semen quality, but uncertain if loose-fitting underwear improves fertility

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Retrieval of sperm

A

Testicular sperm extraction (TESE)

  • Management of obstruction azoospermia
  • Outpatient procedure with LA
  • extract seminiferous tubule tissue

Percutaneous epididymal sperm aspiration (PESA)
- Free sperm is aspirated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q 
Clomiphene citrate (Clomid)
- Mechanism of action
A

Selective estrogen receptor modulator

Blocks ER in hypothalamus –> blocks negative feedback effect of circulating estradiol –> increased GnRH pulse frequency –> increased secretion of FSH (and LH)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Clomiphene treatment regime

A

Can induce withdrawal bleed with progesterone prior if needed
- either spontaneous or induced bleeding

Clomiphene for 5 days from day 2-5
- Typically start day 5, but outcomes comparable
Starting dose 50mg

Ovulation occurs 5-10 days after the last tablet
- Couple advised to have sex every other day

Monitor at least the first cycle with combination of serial USS and serum progesterone levels

Urine pregnancy test 4 weeks post-clomiphene

Subsequent cycles:

  • If ovulation occurs, keep dose the same
  • if doesn’t, increase to 100mg, then 150mg

6 cycles without pregnancy but ovulation occurs = clomiphene treatment failure

23
Q

Clomiphene

outcomes and risks

A

60-85% ovulation rate
30-50% pregnancy rate
- Thought this lower rate due to negative impact that clomid has at endometrium and mucus, Acts primarily as an antiestrogen in the uterus, cervix, vagina
Multiples 5-7%

Risks

  • OHSS <1%
  • Limit lifetime usage to 12 cycles - risk of borderline ovarian tumours

Side effects

  • Hot flushes
  • Headaches
  • Eye effects
  • N/V
24
Q

Infertility management in PCOS

A

Clomiphene or letrozole first

If failed or resistant, and anovulatory with no infertility factors, then gonadotrophins or laparoscopic ovarian drilling

If no pregnancy but ovulating –> IVF

25
Q

Aromatase inhibitors

- mechanism of action

A

Letrozole
- First line in PCOS

inhibiting the conversion of circulating androgens to oestrogens –> reduced negative feedback –> increased FSH

Shorter half life compared to Clomid
Not teratogenic

Safe and very effective in OI (better than clomiphene)
- No data to suggest cancer risk so far - unlikely given very different mechanism of action to clomiphene

26
Q

Aromatase inhibitors

- Regime

A

2.5mg for 5 days on days 2-6
- Increase dose if don’t ovulate to 5mg, then max 7.5mg
Careful instruction and tight monitoring
Generally not more than 6 months

27
Q

Aromatase inhibitors

- outcomes

A

Better mono-ovulation rate, less multiple pregnancies

Cochrane 2018 - aromatase inhibitors for ovulation induction in PCOS

  • Better live birth rate and pregnancy rates compared with clomiphene (27.5% vs. 19.1%)
  • No difference in OHSS rates

Similar effects to laparoscopic ovarian drilling

28
Q

Metformin
- Mechanism of action

and outcomes

A

Insulin sensitising agent
Increased insulin mediated uptake by liver and smooth muscle

In PCOS the aim is to reduce hyperinsulinaemia

Used as adjuvant treatment
- Hasn’t been shown useful as OI alone

Cochrane - metformin for OI in women with PCOS 2019
- Metformin may be beneficial over placebo, but more women probably experience GI side effects
With clomiphene citrate
- Inferior to CC
- BMI <30 - added to CC –> increased pregnancy rate and reduced miscarriage rates with no change to live birth rate

29
Q

Laparoscopic ovarian drilling (LOD)

- mechanism of action

A

Not clear, but hypothesised that get decreased production of androgens due to stromal damage
- Serum LH and testosterone fall, FSH rises

Make 4 holes in ovary with diathermy, only need to do on one side (from RCT findings)

30
Q

Outcomes and risks of ovarian drilling

A

Consider as second line therapy in PCOS, if clomiphene resistant with anovulatory infertility and no other infertility factors

May result in singleton birth in women
No convincing evidence of inferiority over other methods of OI
No increased risk of multiples
No risk of OHSS

ISSUES
Cost
Expertise required for use in ovulation induction
Intra-operative and post-operative risks are higher in women who are overweight and obese
May be a small associated risk of lower ovarian reserve or loss of ovarian function
Peri-adnexal adhesion formation may be an associated risk

31
Q

Gonadotrophins for OI

  • mechanism of action
  • outcomes
  • issues
A 
Recombinant FSH (rFSH) 
- FSH only for PCOS
LH and FSH for hypogonadotropic hypogonadism
Direct stimulation of ovaries

Overcomes negative endometrial impact of clomiphene

RCT - higher pregnancy and LBR compared to clomiphene
Highly successful in inducing ovulation (>95%)

Issues

  • Cost
  • Requires surveillance - bloods and USS
  • More involved
  • Expertise required
  • Increased multiple pregnancy rate (15%)
  • Increased OHSS rate
32
Q

OI and cancer

A

Nulliparity doubles the risk of ovarian cancer
Subfertile women who later give birth do not have an increased risk of ovarian malignancy
Available evidence does not suggest a link between OI drugs and ovarian cancer
Possible weak link with borderline ovarian tumours in later life
- Limit CC to 6 months

33
Q

Complications of ART

A

Ectopic pregnancy - rate 1-4% with IVF

Acute complications

  • Cyst accidents
  • Intra-operative injury
  • OHSS
  • Infection
  • Psychological effects

Pregnancy complications

  • GDM
  • Poly- or Oligohydramnios
  • Multiple pregnancy - MC pregnancy rates 0.9-2% vs. 0.4% for spontaneous conceptions
  • PTB
  • Low birth weight
  • Risk of abnormalities of placentation - abruption, praevia, Vasa praevia
  • Gestational HTN
  • PPH
  • VTE
34
Q

Complications for the child of ART

A

Congenital defects

  • 30-40% increase in risk of major congenital abnormalities compared to normally conceived children
  • Risk greater than for ICSI than IVF

Long-term adult disease - diabetes, HTN

Neurodevelopmental outcomes are similar

35
Q

Prediction of IVF success

A

Overall LBR per embryo transfer 27.3%
Change of live birth following IVF treatment falls with rising female age
from 4th cycle chance of live birth falls as the number of unsuccessful cycles increases
IVF is more effective in those who have previously been pregnant, particularly those who have had a live birth
BMI ideally 19-30
>1 unit of alcohol/day reduces effectiveness
Maternal or paternal smoking can adversely affect success rates
Ovarian reserve based on AFC or AMH
Hydrosalpinx - associated with poor implantation and low pregnancy rates and early pregnancy loss
Submucosal fibroids - decrease the change of success
Endometrial polyps - uncertain, reasonable to remove prior
Endometriosis - prolonged down-regulation with GnRH agonist 3-6 months prior to IVF improves clinical pregnancy rates

36
Q

Steps in IVF treatment cycle

A
  1. Pre-treatment evaluation
  2. Controlled ovarian stimulation using gonadotrophins and GnRH analogues (agonists or antagonists)
  3. Monitoring follicular development using TV-USS +/- serum estradiol levels
  4. Oocyte maturation using hCG
  5. Egg collection and sperm production or sperm recovery
  6. Fertilisation (IVF / ICSI) and subsequent embryo culture
  7. Fresh embryo transfer into the uterus and cryopreservation of surplus good quality embryos
  8. Luteal support through progesterone administration
37
Q

Pros and cons of short over long protocol for IVF

A

Shorter treatment duration
- Convenient for patients
Avoidance of pituitary down regulation
Lower risk of OHSS with similar rates of fertilisation

On average, one less egg obtained per woman per oocyte collection

Long protocol - 2-3 weeks of down regulation before hand

38
Q

Brief description of short protocol for IVF

A

Meds are started at the start of the menstrual cycle in which IVF is performed
Gonadotropins (rFSH) administered in early menstrual phase (cycle day 2)
GnRH antagonists are administered from cycle day 6
- to prevents premature LH surge

Trigger injection is administered to induce final maturation of the oocytes
- Given when 2 or more leading follicles measure 17-19mm

Recombinant hCG
GnRH agonist (reduces OHSS by >80%)

Oocyte collection is arranged 36h after trigger

39
Q

Oocyte retrieval risks

A

1/1500 overall risk of serious complication:

Pelvic infection

  • Increased in patients with endometriosis
  • no evidence prophylactic antibiotics reduces this risk

Bleeding

  • Usually from the vaginal epithelium
  • Rarely from the iliac vessels
40
Q

Fertilisation of oocyte

A

IVF

  • ~100,000 sperm added to each egg
  • Embryo culture from fertilisation to blastocyst stage (usually day 5, sometimes day 6)
  • Fertilisation, as determined by the presence of two pro nuclei (2 PN), is assessed at 20 hrs post-insemination
41
Q

ICSI outcomes

A

Fertilisation rates for ICSI are 60-70%

IVF gives better fertilisation results than ICSI in couples with non-male subfertility
Pregnancy rates after IVF and ICSI are not significantly different

42
Q

Steps of IUI

A

If doing ovulation induction:

  • Oral anti-estrogens taken for 5 days
  • If gonadotrophins used, sc injections are given for 7-10 days

USS is used to monitor response
- Want 1-3 suitably sized follicles with one dominant follicle
Injection of hCG to trigger ovulation
Insemination of prepared sperm sample 24-36h after hCG trigger injection

  • If 2-3 ovulatory follicles present, insemination not undertaken to reduce risk of multiple pregnancy
43
Q

Embryo cryopreservation

A

Vitrification = Ultra-rapid cooling

  • Survival >90%
  • Can be stored indefinitely in liquid nitrogen
44
Q

Preimplantation genetic testing

A

In NZ, publicly funded if >25% chance of being affected by serious inherited genetic disorder
Indications
- Advanced oocyte age - Reduces risk of miscarriage or baby born with aneuploidy
- Chromosomal structural rearrangements
- Monogenic disease risk reduction

45
Q

Incidence of OHSS

A

Mild OHSS occurs in 33% of ART cycles

Severe requiring hospitalisation in 0.3%

46
Q

Pathophysiology

of OHSS

A

Systemic disease resulting from vasoactive products released by hyperstimulated ovaries
production of proinflammatory cytokines

Increased capillary permeability
Leakage of fluid from vascular compartment
Third-space fluid accumulation
Intravascular dehydration

47
Q

Investigations in OHSS

A 
FBC (haematocrit)
Albumin - low
LFTs - may be elevated
U&Es - hyponatraemia, hyperkalaemia
Creatinine
CRP
Serum osmolality (hypo-osmolality)
Coagulation profile
HCG
USS
48
Q

OHSS more commonly associated with

A

Patient factors

  • Young age
  • PCOS
  • Diabetes
  • Previous OHSS
  • Conception
  • Increased in multiple pregnancy
  • Increased AFC
  • High levels AMH

Treatment factors

  • High follicular phase LH
  • High-dose gonadotrophin stimulation regimens
  • Use of GnRH analogues > antagonists
  • Multiple follicular response
  • High serum estradiol levels during treatment
  • Exposure to hCG (as trigger)
  • Number of oocytes retrieved in IVF - Risk increases with increasing number
49
Q

Strategies to lower the incidence or severity of OHSS

A

Using low-dose stimulation protocols, or natural-cycle IVF
Follicular monitoring
Utilising GnRH antagonist cycles (short protocol)
Utilising progesterone instead of hCG for luteal support
Abandoning ART cycles prior to hCG administration and oocyte collection if too many follicles
Delaying embryo transfer following collection and elective freezing of all embryos
Metformin for PCOS patients
Routine single embryo transfers
Coasting - hCG trigger is withheld until serum estradiol levels have returned to acceptable levels
Cabergoline (dopamine agonist) may be used to reduce OHSS incidence in high risk women

50
Q

Classification of severity

A

Mild OHSS - Ovarian size usually <8cm3

Severe OHSS

  • Clinical ascites (+/- hydrothorax)
  • Oliguria (<30ml/h)
  • Haematocrit >0.45
  • Hyponatraemia, Hyperkalaemia (>5 mmol/l)
  • Ovarian size usually >12cm3

Critical OHSS

  • Tense ascites / large hydrothorax
  • Oliguria / anuria
  • Thromboembolism
  • ARDS
  • Haematocrit >0.55
  • WCC >25 000/ml
51
Q

Outpatient Management

of OHSS for mild or moderate OHSS, select severe OHSS

A

Self-limiting in the majority of women (resolves over a period of 7-10 days)
Give verbal and written info, contact details
Avoid injury to enlarged ovaries (e.g. strenuous physical activity, sex)
Drink to thirst rather than set amount (>1L/day)
To reduce VTE risk, mobilise and avoid strict bed rest
Ideally record fluid input-output
Daily weight
Avoid NSAID
Review every 2-3 days unless signs / symptoms of worsening OHSS

Hospital admission should be considered::

  • Are unable to achieve satisfactory pain control with simple analgesics
  • Intractable vomiting
  • Are unable to maintain adequate fluid intake due to nausea
  • Show signs of worsening OHSS despite outpatient intervention
  • Are unable to attend for regular outpatient follow up
  • Have critical OHSS
  • Need IVF, analgesia
  • SOB
  • hct >0.45, electrolyte disturbance
52
Q

Inpatient management of OHSS

A

MDT
Monitoring
- Body weight, abdo girth, fluid balance - daily
- FBC, hct, serum electrolytes, osmolality, LFTs - daily
Fluid management
- Encourage oral fluids
- UO - aim >30-50ml/hr

Analgesia
- Paracetamol, oral opiates
- NSAIDs contraindicated
VTE prophylaxis

Paracentesis of ascitic fluid :

  • Severe abdominal distension and pain
  • SOB and respiratory compromise
  • Oliguria despite adequate volume replacement, secondary to increased abdo pressure –> reduced renal perfusion

Consider IV colloid therapy for women who have large volumes of fluid removed by paracentesis

Pelvic USS if suspect torsion

53
Q

CPAC Criteria

A 
Exclusion criteria:
	- Female age >40y
	- Male age >55y
	- Either partner current smoker
	- Female BMI >32
If stored embryos from a previous private IVF cycle, these embryos must be used, before a further publicly funded IVF cycle is initiated
CPAC threshold 65 points
Up to two packages of care available
- 1 package could be 4x IUI or 1x IVF cycle
Current wait time ~12-15 months for IVF

Anna and louise (28 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions