Dr nidhi Outcome of IVF, Ppt
                     Dr. Nidhi Sharma
JISNH,   28/03/12
OBSTETRIC 
OUTCOME OF IVF 
Introduction
 Rate of IVF-ICSI increasing- 1.3-4.2% of all births
 Approx 1 million children borne out of IVF in USA
 Risk of following complications also continuously 
increasing:
       miscarriages
       Birth defects
       multiple pregnancy
       gestational diseases
       Prematurity, LBW, IUGR & PTB
       Increased operative deliveries
Early pregnancy loss
 Biochemical pregnancy- failure to 
demonstrate an embryonic sac on USG in a 
patient with β-hcg positive in blood or urine
 Blighted ovum- failure to demonstrate a fetal 
pole in a patient in which gestational sac is 
visible
 Missed abortion- Failure to demonstrate a 
heart beat in a foetus
 18-22% of all spon pregnancies
 12-48% in all ART pregnancies
                     EPL
    
   
Singletons after IVF
Tummers et al,2004
Twins after IVF
                   EPL
     A small increase in sp abortions after ART is there 
which primarily is related to the underlying causes of 
infertility and rather than the procedure( Wang et al 2004)
   Is the fertility treatment itself a risk factor for early   
pregnancy loss? Ragaa et al. 2011 
it is concluded that even after adjustment for confounding factors 
conception through FET remained an independent risk factor for 
EPL. Other modes of conception were not related with EPL
  Ectopic pregnancy in 
IVF
 General population-2%
 ART- 2-8%
 After tuboplasty- upto 40% depending upon extent, 
site and type of surgery done
 After recanalisation-6%
 Heterotopic preg-1:100 to 1500 in ART as 
compared to 1: 30000 spon preg
 Cervical pregnancy
    Risk factors for EP
 Spon pregnancies        ART
  
 Prev EP  Tubal disease
 PID  Endometriosis
 Tubal disease/  Specific ART 
surgery procedure
 Smoking  Embryo implantation 
 Age>35 potential
Other possible risk 
factors
 Blastocyst transfer? 
 Assisted Hatching?
 Frozen embryo transfer?
 Deep fundal transfer?
 High transfer volume?
 Multiple embryo transfer?
 
 None of the above are found to have any 
effect on occurrence of EP
Ectopic pregnancy after assisted reproductive 
technology: what are the risk factors?
Chang, Hye Jina,b; Suh, Chang Sukb,c,     curr opin,2010
Summary: Different hormonal milieu, the 
reproductive health characteristics of infertile 
women such as distorted tubal function, technical 
issues of IVF procedures, and the estimated 
embryo implantation potential are possible risk 
factors. How each factor contributes to the risk of 
occurring ectopic pregnancy after assisted 
reproductive technology is uncertain and needs 
further investigation
    
        Ectopic Pregnancy in IVF
 Laparoscopic salpingectomy in
     hydrosalpinges enhances the success of
     IVF (Strandell 2000; Johnson 2002)
 
 ART do not increase the risk of EP,
    however specific characteristics of the
    female patients do
   Multiple pregnancy In 
IVF
  Spon pregnancies             ART
 Rate- 3.26%  Rate- 26.4%
 Twins- 1in  Twins- 1 in 60 to 70
100deliveries
 Triplets- 1 in 1000  Higher order- 3-4 times 
 Quadruplets- 1in 10000 increase
 Monozygous 

twinning(30%) - MZ- 5-10 times increase

3.5/1000 Transfer of higher No of 
embryos inc risk of DZ 
 Dizygous twinning as well as higher order 
(70%) gestations(MZ less)
  US data
 3.26% of all births
 60% from natural conceptions
 21-32% from OI/SO
 8-16% from ART
  
Higher order gestation- 20% from natural
                                    39-67% from OI/SO
                                    13-44% from ART
 
 Higher order are generally polyzygotic
 Cochrane review 2009 has not found 
asso with AH
 No association with Blastocyst transfer
 No association with the type of culture 
medium
Maternal risks in MP
  Perinatal risks
Fertil steril 2012
  Multiple pregnancy
 Is there a difference in outcome of sp conceived Vs 
ART conceived twins?
 
    Conflicting results
 Singletons after Ivf have worse outcome than SC but 
multiples have 40% lower risk of morbidity (Helmerhorst et 
al,2005)
 No diff in morbidity ( Shebl et al2005)
 Risk of prematurity & SGA are comparable after controlling 
for MZ along with other maternal factors & concluded that 
worse outcome in SC twins could be due to more No of 
MZ( Andrea et al.2002)
  vanishing twin 
syndrome
 Disappearance of one of the two gestational 
sacs or the embryo after documented fetal 
activity is known
 Incidence- 12-38%
 Survivor twin more affected when demise 
occurs >8wk (MC twins)
 
            
 Perinatal risks
  Effect of OHSS on 
pregnancy
     Obstetric outcome of in vitro fertilized 
pregnancies complicated by severe ovarian 
hyperstimulation syndrome: a multicenter study. 
                              Yoram Abramov, M.D,2002
   
    Conclusion(s): Among patients who have severe 
OHSS after IVF treatment, the pregnancy rate and the 
rates of multiple gestation, miscarriage, prematurity, low 
birth weight, pregnancy-induced hypertension, gestational 
diabetes, and placental abruption are significantly higher 
than those reported previously for pregnancies conceived 
with the use of assisted reproductive techniques
   
  Are these pregnancies more 
complicated?
  Gestational diseases in ART  
pregnancies
   Metaanalysis (age matched)
  12283 IVF singletons + 1.9 mill SC singletons
 Placenta praevia ↑ OR 2.9 (1.5-5.4)
 Gestational diabetes ↑ OR 2.0 (1.4-3.0)
 Preeclampsia ↑OR 1.6 (1.2-2.0)
           (Jackson, Obstet Gynecol 2004)  
 Gestational diseases in 
ART
Multivariate logistic regression analysis
36062 singletons: SC 32286, ovulation
induction 1222, IVF 554
 
 Ovulation induction                 IVF
Placental abruption↑          Placenta abruptio↑
Fetal loss >24 wks ↑           Placenta praevia ↑
Gestational diabetes ↑       preeclampsia↑
                          (Shevell, Obstet Gynecol 2005)
   Subfertility and adverse outcome
 Subfertility correlates with adverse 
outcome (Henriksen, OG 1997; Pandian, HR 2001; Basso, HR 
2003; Thomson, OG 2005; Zhu, BMJ 2006)
 Perinatal mortality and time-to-pregnancy >12 
months    (Draper, Lancet 1999; Basso, HR 2005)
  Gestational diseases in ART
 Cochrane review 2006- ( levelIA)
 Preg achieved by IVF/ICSI are at higher risk for Obs 
& Perinatal complications than SC.
 Increased incidence of Pl. Previa, Placental 
insufficiency, Abruptio, PIH/ PE or Prematurity
 Close surveillance duirng preg should be considered
 It is unclear whether inc risk is due to underlying 
infertility, charac. of infertile couple or use of ART
 Higher operative delivery
 Higher risk of LBW & SGA
  
ASRM press release 2011
 Singleton obs outcome depends upon the tech 
used & the cause of infertility with poorest risk 
factor for prematurity & LBW being uterine 
environment
 Gobbon et al 2006- (review of SART data)
    All types of female infertility except unexplained 
associated with PTB & LBW, uterine factor being 
poorest
    Male factor was not associated with LBW
Does Perinatal outcome varies with the 
number of embryos transferred?
Elective single embryo transfer and perinatal outcomes: a 
systematic Rosheen Grady et al, fertil steril 2012
review and meta-analysis
Result(s): Sixteen studies were included (eight RCTs, eight cohort studies). 
Compared with DET-conceived infants, eSET-conceived singletons were less
likely to be born either preterm (RCT-based relative risk [RR] 0.37, 95% 
confidence interval [CI] 0.25–0.55) or with LBW (RCT-based RR 0.25, 95% CI 
0.15–0.45; cohort study RR 0.51, 95% CI 0.29–0.91). However, compared with 
spontaneously conceived singletons, eSET gestations had higher risks of PTB 
(RR 2.13, 95% CI 1.26–3.61), placenta previa (RR 6.02, 95% CI 2.79–13.01), 
gestational diabetes (RR 1.69, 95% CI 1.19–2.42), and ectopic pregnancy (RR 
6.40,95% CI 4.38–9.35).
Conclusion(s): Elective single embryo transfer is associated with decreased 
risks of PTB and LBW compared with DET but higher risks of PTB compared
with spontaneously conceived singletons
 possible explanations for poorer 
outcome
 Infertility alone
 IVF procedure itself
 Heightened monitoring or intervention by health 
care providers
 Placenta previa occurs more often in singletons 
borne out of SET or DET  while abruptio is more 
common in SET singletons as compared with spon 
conceived ( Antonio et al,Hum reprod,2010)
  Growth and development of Ivf 
children
Data scarce with conflicting results as long term studies still 
underway
1)   Birth defects in ART- slightly increased
    
    Hansen et al,2005 - risk increased by OR 2 even after 
controlling for confounding factors like maternal age, parity & 
sex of baby 
      
    Katalinic et al,2004- OR of 1.2% for CMF but risk goes down 
after controlling for other factors 
   
   
        Birth defects
 No increased risk in multiple preg.(indirectly 
through inc in monozygosity)
 No increase in CMF in ICSI as compared to IVF
                                                           ( Bonduelle et al.1998)
 Causes-  Technique?
                   Genomic Imprinting disorders
                   Subfertility per se
   Birth defects
 Genomic imprinting disorders higher in ART
      -  Beckwith-wiedemann syd
      -  Angelman syd
Possible causes-
      - effect of in-vitro culture conditions?
     - severity of male factor infertility?
     - subfertility per se?
2. Childhood cancers- no increased risk
3. Growth & physical development- no significant 
difference
4. Neurological sequelae- cerebral palsy & 
epilepsy have found to be increased in few 
studies(Ericson et al2002,Stromberg et al 2002) ,but more related 
to LBW & LGA.
5. Pubertal development & fertility- can be a concern 
as in-utero elevated sex steroids exposure is 
found in ART pregnancies.
7. Genetic risks of ICSI- 
 Concern arises due to use of naturally unselectd 
sperm for insemination
 Men with azoo or s. Oligo have 5.8% incidence of 
ch. Anomalies
 Klinefelter’s syd is MC abnormality in Azoospermia
 Offsprings have a slightly increased risk for sex 
chromosome aneulpoidy
 Proper genetic counselling & screening must 
before undergoing ICSI for severe male factor 
infertility