The document discusses various risks associated with pregnancies resulting from assisted reproductive technologies (ART) like IVF. It notes that ART pregnancies have slightly higher risks of early pregnancy loss, ectopic pregnancy, multiple pregnancies, gestational diseases, birth defects, and poorer perinatal outcomes. However, it also states that some of these risks may be due to underlying infertility issues rather than the ART procedures themselves. The document advocates for close monitoring of ART pregnancies and suggests more research is needed to fully understand all risk factors.

1. 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 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

4. EPL
Tummers et al,2004
Singletons after IVF

5. Twins after IVF

6. EPL
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
 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

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-1:100 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
- Age>35
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 >8wk (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 >24 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 >12
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] 0.25–0.55) 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

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
 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