Embryo development Day 0 Day 1 Day 2 Day 3 Day 4 Day 5 Day 6

to reduce the risk of multiple pregnancies Embryo transfer Replacing 1-2 embryos to reduce the risk of multiple pregnancies

IVF An effective treatment for different causes of infertility Live birth rate 30-50% ~25-30% of embryos will implant

Factors affecting IVF success Age of women Number of treatment cycles Ovarian response Others: smoking, obesity, hydrosalpinges, uterine fibroids etc. Endometrial receptivity

Complications Ovarian stimulation Egg collection Embryo transfer Ovarian hyperstimulation syndrome (OHSS) Ovarian carcinoma Egg collection Bleeding Pelvic infection Embryo transfer Multiple pregnancy Ectopic pregnancy Psychological

Reduction of multiple pregnancy Reducing the number of embryos replaced i.e. replace SINGLE embryo or blastocyst Fetal reduction

1+1 Vs 2 embryos 1+1 (n=330) 2 (n=331) P value Live births Fresh cycle 91 (27.6%) 142 (42.9%) <0.001 Frozen cycle 29 (16.4%) ---- Cumulative cycles 128 (38.8%) NS Multiple births 1 (0.8%) 47 (33.1%) (Thurin et al., NEJM, 2004)

OHSS 5 % moderate (Delvigne 2002) 2% required hospitalization (Papanikolauo 2005) Life-threatening condition Estimated mortality 3/100,000 cycles

OHSS Ovarian enlargement and abdominal distension Nausea, vomiting & abdominal pain Decrease in urine output Ascites, hydrothorax & generalized oedema Haemoconcentration & thromboembolism Liver failure and renal failure

OHSS management Reduced by identifying high risk patients and choosing appropriate stimulation protocols (GnRH antagonist protocol, mild stimulation, progesterone for luteal phase support) In cases of excessive response – agonist to induce LH surge in antagonist cycles, freeze all embryos, hydroxyethyl starch and cabergoline

OHSS-Principles of management Careful monitor of vital signs, BW, abdominal girth, CBP, Hct, RFT, LFT, clotting studies Pelvic U/S to assess ascites & ovaries CXR if respiratory symptoms or signs Mild/moderate can be managed as outpatient Paracetamol/codeine for pain; avoid NSAID Admit for inpatient management in severe cases

OHSS-Principles of management Adequate fluid intake – IV fluid (N/S and colloids) if the patient cannot tolerate oral fluid Diuretics should be avoided unless oliguria persists despite adequate intravascular expansion and under careful haemodynamic monitoring U/S guided paracentesis in case of tense ascites Anticoagulation should be considered in patients admitted for severe or critical OHSS

Congenital abnormalities ~30% increase in the risk of birth defects following IVF (Hansen et al., HRU, 2013) Higher rate of de-novo chromosomal anomalies in ICSI offsprings (1.6% Vs 0.5%) mainly higher no. of sex chromosomal anomalies and partly a higher no. autosomal structural anomalies (Bonduelle et al., 2002)

1.32 (1.24, 1.42)

Neonatal outcomes of singletons following ART Vs spontaneous conceptions Relative risk (95% CI) Very preterm (< 32 weeks) 3.27 (2.03 to 5.28) Preterm (< 37 weeks) 2.04 (1.80 to 2.32) Very low birth weight (< 1500 g) 3.00 (2.07 to 4.36) Low birth weight (< 2500 g) 1.70 (1.50 to 1.92) Small for gestational age 1.40 (1.15 to 1.71) Caesarean section 1.54 (1.44 to 1.66) NICU admission 1.27 (1.16 to 1.40) Perinatal mortality 1.68 (1.11 to 2.55) (Helmerhorst et al., BMJ, 2004)

Longterm health outcomes May increase the incidence of high blood pressure, elevated fasting glucose, total body fat composition, advancement of bone age and potentially subclinical thyroid disorder Increase the incidence of cerebral palsy and neurodevelopmental delay related to prematurity and low birthweight Potential increase in the prevalence of early adulthood clinical depression and binge drinking (Hart and Norman, HRU, 2013)

Thank you for attention