Dr Nidhi Outcome of IVF | Jindal IVF Chandigarh

1
Obstetric Outcome of IVF

• Dr. Nidhi Sharma
• JISNH, 28/03/12

2
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

3
Early pregnancy loss

• Biochemical pregnancy- failure to demonstrate an
  embryonic sac on USG in a patient with ß-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

4
EPL

Singletons after IVF
Tummers et al,2004
5
Twins after IVF
6
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
7
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-1100 to 1500 in ART as compared
  to 1 30000 spon preg
• Cervical pregnancy

8
Risk factors for EP

• Spon pregnancies
• Prev EP
• PID
• Tubal disease/ surgery
• Smoking
• Agegt35

• ART
• Tubal disease
• Endometriosis
• Specific ART procedure
• Embryo implantation potential

9
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

10
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
11
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

12
Multiple pregnancy In IVF

• Spon pregnancies
• Rate- 3.26
• Twins- 1in 100deliveries
• Triplets- 1 in 1000
• Quadruplets- 1in 10000
• Monozygous twinning(30) - 3.5/1000
• Dizygous twinning (70)

• ART
• Rate- 26.4
• Twins- 1 in 60 to 70
• Higher order- 3-4 times increase
• MZ- 5-10 times increase
• Transfer of higher No of embryos inc risk of DZ
  as well as higher order gestations(MZ less)

13
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

14

• 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

15
Maternal risks in MP
16
Perinatal risks
Fertil steril 2012
17
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)

18
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
  gt8wk (MC twins)

19
Perinatal risks
20
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

21

• Are these pregnancies more complicated?

22
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)

23
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 gt24 wks ? Placenta praevia ?
• Gestational diabetes ? preeclampsia?
• (Shevell, Obstet
  Gynecol 2005)

24
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 gt12
  months (Draper, Lancet 1999 Basso, HR 2005)

25
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

26
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

27
Does Perinatal outcome varies with the number of
embryos transferred?
28
Elective single embryo transfer and perinatal
outcomes a systematic review and meta-analysis
Rosheen Grady et al, fertil steril 2012
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 0.250.55) or with LBW
(RCT-based RR 0.25, 95 CI 0.150.45 cohort
study RR 0.51, 95 CI 0.290.91). However,
compared with spontaneously conceived singletons,
eSET gestations had higher risks of PTB (RR 2.13,
95 CI 1.263.61), placenta previa (RR 6.02, 95
CI 2.7913.01), gestational diabetes (RR 1.69,
95 CI 1.192.42), and ectopic pregnancy (RR
6.40,95 CI 4.389.35). 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
29
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)

30
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

31
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

32
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?

33

• 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.

34

• 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
• Klinefelters 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