Reproductive stuff Flashcards

Question

Aromatase inhibitors | - mechanism of action

Answer 1

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

Answer 2

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

Answer 3

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

Answer 4

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

Answer 5

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)

Answer 6

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

Answer 7

``` 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

Answer 8

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

Answer 9

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

Answer 10

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

Answer 11

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

Answer 12

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

Answer 13

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

Answer 14

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

Answer 15

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

Answer 16

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

Answer 17

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

Answer 18

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

Answer 19

Vitrification = Ultra-rapid cooling - Survival >90% - Can be stored indefinitely in liquid nitrogen

Answer 20

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

Answer 21

Mild OHSS occurs in 33% of ART cycles | Severe requiring hospitalisation in 0.3%

Answer 22

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

Answer 23

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

Answer 24

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

Answer 25

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

Answer 26

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

Answer 27

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

Answer 28

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

Answer 29

``` 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 ```