Management of twin pregnancies after ART

1. Chairperson: Haryana Chapter Of ISAR ,2011-2015
Executive member ISAR 2016-2017
Associate RCOG
Director: LOOMBA HOSPITAL AND IVF CENTRE ,
Ambala Cantt. HARYANA since 1988
Ex consultant at central hospital ,Arar,
Saudi Arabia
Ex senior resident Ganga Ram Hospital
New Delhi.
Graduate from GOMCO ,Patiala.1985.
Awards: President’s gold medal at university level.
Affiliations: ASRM,RCOG,FOGSI,ISAR,ACOG,,IAGE,
ASPIRE,Foetal Medicine Foundation
regular attendee at many national
and international conferences.
Achievements: First IVF/ART centre in haryana in 2003
Trained at CLEVELAND CLINIC U.S.A in
IVF/ICSI
Trained at HARVARD in advanced
ultrasound in fetal medicine
Advanced laparoscopy training at Kiel,
Germany.
Specialised : Infertility/ART, Fertility related
Fields Laparoscopic surgeries, Fetal medicine
Recurrent pregnancy loss
www.loombahospital.
com
Dr.Poonam Loomba
M.D.
loombapoonam
@gmail.com
www.loombaivf.com

2. Twin Pregnancy
Poonam Loomba, M.D.
Loomba Hospital and IVF Centre
Ambala Cantt.

3. Background of this discussion
Although multifetal births account for only 3% of all live
births, they are responsible for a disproportionate share of
perinatal morbidity and mortality
Survivors of preterm births have an increased risk of mental
and physical handicap.
Maternal morbidity increases.
Hospital costs increase by 40%
NICU Admissions :1/4th of twins for 18 days .

5.  In naturally-conceived multiple gestation, the
prevalence of dizygotic twinning varies with
ethnicity (1.3 per 1,000 in Japan, 8 per 1,000 in
the U.S. and Europe, and 50 per 1,000 in
Nigeria)
 Dizygotic twinning is also associated with
increasing maternal age, greater parity, and a
maternal family history of twinning .
 Monozygotic twinning is relatively constant (4
per 1,000 live births) although genetic
predisposition may have some influence.

6. Kodhini:Seeing double in India’s Twin
town by Jordi Pizzaro

7. Role of ART in Twin Pregnancy?

8. National ART Registry of India 2013/2014
• 2013: Self cycles: 72.24% S /24.79% T
• 2014: Self cycles: 71.65% S /25.46%T
• 2013: Donor eggs: 61.34% S/32.13%T
• 2014:Donor eggs: 61.52%S/32.78%T
• 2013:ED: 60.94%S/26.99%T
• 2014:ED:60.73%S/30.73%T
• 2013:Surrogacy:76.98%S/21.3%T
• 2014:Surrogacy:71.75%S/26.50%T

9. The incidence of twins among births from SO and
ART is more than 20 times greater than for births
resulting from natural conception, and that of
high-order multiple gestation is more than 100
times higher { ASRM File}

10. Multiple follicular development is the dominant risk factor
for dizygotic twinning and high-order multiple gestations in
OI and SO cycles, and it can be difficult to prevent . It also
increases the risk of monozygotic twinning by two- to
threefold .
Transfer of more than one embryo .
The risk of monozygotic twinning may be increased by
approximately twofold in conventional IVF cycles and
increases further in ART cycles involving ICSI ,extended
cultures.
A 2009 Cochrane review of four studies with a total of 524
patients concluded that available data were insufficient to
determine whether assisted hatching increased the risk of
monozygotic twinning .

11. Any relationship with type of drugs
used for OI/ SO?
• Clomiphene
• Gonadotropins

12. Dose of clomiphene was positively related to pregnancy rates
and birth rates, but not to multiple birth rates, abortion or
ectopic pregnancies. Doses >100 mg/day were responsible for
16% of births and 11% of multiple births. Doses >100 mg were
required for pregnancy in 27% of women who weighed >90 kg
(198 lb), compared to 11% who weighed 45–59 kg (100–131 lb)
(Table I). Doses of 25 mg were enough for pregnancy in 3% of
women.
Twin births occur in ~10–12.3% of clomiphene pregnancies,
according to information from series comprising ≥1000 births. In
the original study conducted during the 1960s (Macgregor et al.,
1968)
Multiple pregnancies were unrelated to clomiphene dose in our
series and also in that of Groll (1984), who analysed the
outcome of 700 clomiphene pregnancies from his practic

13. ASRM FACT SHEET
When using injectable gonadotropins alone or with IUI, up
to 30% of pregnancies are associated with multiple
implantations (twins or more), which only occur in 1% to
2% of naturally occurring pregnancies. The increased risk
of multiples is due to the number of eggs that are
stimulated during an ovulation induction cycle or due to
the number of embryos transferred in an IVF cycle. While
most multiple pregnancies are twins,

14. Higher incidence of MZT after IVF. Monochorionic-diamniotic
implantations were increased, whereas monochorionic-monoamniotic
were not. The MZT risk factors included young age and extended
culture, but not zona penetration or cryopreservation.

15. Of the 441 clinical intrauterine pregnancies, 314 (71.2 percent)
resulted from the conception of singletons, 88 (20.0 percent) of
twins, 22 (5.0 percent) of triplets, 10 (2.3 percent) of quadruplets, 5
(1.1 percent) of quintuplets, and 2 (0.5 percent) of sextuplets. Low-
order pregnancies (si
Norbert Gleicher, M.D., Denise M. Oleske, Ph.D., Ilan Tur-Kaspa, M.D., Andrea
VidaliM.D., and Vishvanath Karande, M.D.
N Engl J Med 2000;
A correlation matrix revealed that the peak serum estradiol
concentration and the total number of follicles were directly correlated
with the incidence of high-order multiple pregnancy (for peak serum
estradiol concentration: r=0.24, P<0.001; for total number of follicles:
r=0.26, P<0.001). Age was inversely correlated with the incidence of
high-order multiple pregnancy (r=–0.14, P=0.008). There was no
correlation between the number of follicles 16 mm or more in
diameter and the incidence of high-order multiple pregnancies.

16. The inadequate health insurance
plans/reimbursement for ART
encourages the transfer of more
number of embryos in order to
increase probability of pregnancy in
couples with limited financial
resources

17. A couple with one failed IVF Cycle.
They had opted for SET but this time
they want more number of embryos .
Age of woman is 36yrs

18. What are the components of Pre IVF
Counselling?
• Maximum number you can transfer
• Finances/social,cultural, religious values
• Family support
• Diet and Nutrition
• Cryopreservation
• Miscarriage rate
• Fetal reduction
• Complications of multiple pregnancy
• Multidisciplinary approach
• Referral to tertiary care centre

19. Fill in the blanks
1.Dizygotic twinning occurs from ……. eggs and
……. Sperms and constitute …………. of all twins
2.Monozygotic twinning occurs from …….. egg
and …….. Sperm and constitute ………… of all
twins
3.Zygosity refers to………… and Chorionicity refers
to…………………
4.World’s first IVF Twins were born in …………………
5 Lambda sign is diagnostic of .............................

20. 32 yr female conceived in first IVF
Cycle .Twin Pregnancy.
Came at 13 wks with report of
abnormal biochemical markers .Was
advised to discontinue pregnancy.
Couple is educated.

21. 35 Yr female had twin pregnancy
in third IVF Cycle.
11-13 wks scan reported as normal
NTT in both fetuses NB was not
seen in one of the fetuses.
Couple is well educated .

22. Screening in twins by biochemistry alone is considered problematical
by some (Cuckle, 1998), .
Whilst NT can be used successfully to screen in twins with a similar
detection rate and false positive rate to that in singleton pregnancies,
the combination of both first-trimester NT and maternal serum
biochemistry can improve the overall detection rate to around 80%
(Spencer, 2000)
Screening in twin pregnancies requires adjustment of the calculated
MoM to account for the presence of two fetuses. In general, for free β-
hCG, this should be by dividing the observed corrected MoM by 2.023.
For PAPP-A two different factors are required −2.192 in dichorionic
twins and 1.788 in monochorionic twins.
Kevin Spencer1,2*, Karl O. Kagan2,3 and Kypros H. Nicolaides
Prenat Diagn 2008; 28: 49–52

23. In monochorionic (and so monozygotic), both fetuses will be affected
or unaffected. Since the amount of cffDNA is approximately double
that of a singleton pregnancy, cffDNA aneuploidy testing will not only
be possible but probably more effective than in singletons.
In dichorionic, , maternal plasma DNA testing would, in theory, not
be as straightforward.
Two studies of small series of twin pregnancies have suggested that
shotgun sequencing-based approaches are able to detect fetal
trisomies in twin pregnancies. It is also possible to determine the
zygosity of twin pregnancies using targeted sequencing from
maternal plasma. The application of NIPT to twin pregnancies is still
at a very early stage of development
The complexity introduced by twin pregnancies suggests that, prior
to cffDNA testing, a good quality ultrasound scan would be a valuable
first step .
RCOG 2014

24. Background
Prenatal Diagnosis
Amniocentesis
Chorionic villous sampling
: technically difficult to accomplish in patients with multiple
gestation

25. Role of TVS in first trimester

26. Chorionicity assessment
before 10 weeks?
• Number of Yolk Sacs
• Number of GSAC
• Number of amniotic sacs in chorionic cavity

27. After 10 weeks?
• Sex discordance
• No of distinct placenta
• Twin peak/lambda sign-results from echodense
chorionic villi between the two layers of chorion
at its origin from the placenta.(100% PPV for DC
placentation)
• T sign:MCDA placentation
• Epsilon sign:TCTA placentation
• Membrane thickness:cutoff 2mm

30. Diagnosing anomalies(excluding nt)
• Anencephaly
• Large encephalocoels
• Holoprosencephaly
• Cystic hygroma
• Omphalocoel/gastrochisis(size of
protruding ant abd mass>7mm and
persistence beyond 12weeks)
• Amniotic band syndrome
• Conjoined twins

33. Role of ultrasound in 2nd trimester

34. Role of ultrasound in third trimester

35. Twins and preterm birth
Can preterm birth be predicted in
Twin pregnancy?

36. Can preterm labor be predicted in multiple
gestation?
Cervical length Measurement by ultrasonography
- Shortened cervix : predictive of preterm delivery in twin
pregnancies
- Cx length < 25mm (at GA 24wks)
: best predictor of delivery before GA 32, 35 and 37wks.
twin gestations (m/c)
Cervical Length Measurement by Digital Examination
- by experienced examiner
- Less objective than USG, not allow assessment of the internal os
Clinical Considerations and Recommendations

37. Am JOBG:2016 Feb;214(2):277.e1-7. doi: 10.1016/j.ajog.2015.08.065.
Epub 2015 Sep 9.
Transvaginal cervical length scans to prevent prematurity in twins: a
randomized controlled trial.
Gordon MC1, McKenna DS2, Stewart TL3, Howard BC4, Foster KF5, Higby
K6, Cypher RL3, Barth WH7.
This is a multicenter, randomized, controlled trial of 125 dichorionic or
monochorionic/diamniotic twin pregnancies without prior preterm birth <28
weeks. The study group (n = 63) had TVCL and digital exams monthly from
16-28 weeks and were managed with a standard
algorithm for activity restriction and cerclage. The control group (n =
62) had monthly digital cervical examinations but no routine TVCL
ultrasound examinations. The primary outcome was gestational age at
delivery. Secondary outcomes included percentage of deliveries <35
weeks, and maternal and neonatal outcomes. Routine second-trimester
transvaginal ultrasound assessment of cervical length is not associated with
improved outcomes when incorporated into the standard management of
otherwise low-risk twin pregnancies.

38. Can preterm labor be predicted in multiple
gestation?Fetal Fibronectin
- high-molecular-weight extracellular matrx glycoprotein
- normally found in fetal membranes, placental tissues and
amniotic fluid.
- in cervical-vaginal fluids>50ng/ml
: abnormal → predict preterm delivery in singleton gestations
Home Uterine Activity Monitoring

39. Other high risk factors for PTB
• Prev h/o PTB ,PPROM,RPL
• Diabetes
• Obesity
• Polyhydramnios

40. 32 yr F ,Twins in 2nd IVF Cycle.TVS for length of cervix
Done.
At 22 wks Short cervix < 2.5 cm .
Couple is well educated and informed.

41. Interventions
• Bed Rest:Crowther 2010
• Prophylactic CC:Dor et al
1982
• USG indicated CC :Berghella
et al 2005
• Vaginal
Progesterone:Norman et al
2009
• Intra muscular
Progesterone:Durnwald et
al 2011
• Tocolysis:Yamasmit et al
2005
• NO
• No
• No
• No
• No
• No

42. Author’s conclusion
In unselected women with an uncomplicated twin gestation,
treatment with progestogens (intramuscular 17Pc or vaginal natural
progesterone) does not improve perinatal outcome. Vaginal
progesterone may be effective in the reduction of adverse perinatal
outcome in women with a cervical length of ≤25 mm; however,
further research is warranted to confirm this finding.
Effectiveness of progestogens to improve perinatal outcome
in twin pregnancies: an individual participant data meta-
analysis. BJOG 2015

43. A randomised controlled double-blind clinical trial of
17-hydroxyprogesterone caproate for the prevention of
preterm birth in twin gestation (PROGESTWIN):
evidence for reduced neonatal morbidity. BJOG 2015
ONCLUSIONS:
Intramuscular 17OHPC therapy did not reduce PTB before
37 weeks of gestation in unselected twin pregnancies.
Nonetheless, 17OHPC significantly reduced neonatal
morbidity parameters and increased birthweight.

44. RCOG Green top guidelines 2011
• In Singleton pregnancy with h/o PTB or RPL in
second trimester ultrasound indicated cervical
cerclage can be offered if length of cervix is
<2.5cm

45. Cervical cerclage in twin preg
• The insertion of a history- or ultrasound-
indicated cerclage in women with multiple
pregnancies is not recommended, as there is
some evidence to suggest it may be
detrimental and associated with an increase in
preterm delivery and pregnancy loss.

46. Steroid cover
• Dosage
• When to give
• Once or twice

47. Serial ultrasounds for monitoring
length of cervix
• How frequent?
• What Route?

48. Prevention of PPROM
• Endo cervical cultures/Screening for
BV/Chlamydia/Gonorrhoea
• HVS Cultures
• Antibiotics/Metronidazole

49. 41 yr old female .Comes at 23 wks.Conceived with
donor oocytes.
Discordant growth from early GA. Normal 11-13 wks
scan. Oligohydramnios in one sac with growth
restriction in both fetuses .
How do you define discordant growth?
What else would you like to check on her so as to
explain her the possible prognosis of this
pregnancy?
• Best method for fetal surveillance?
• What if one fetus dies in utero?
• With efficient surveillance till what GA you can
prolong pregnancy?

50. • Discordant fetal growth is defined as 15-25%
reduction in the EFBW of the smallest fetus
compared to the largest(Talbot et al 1997).>18%
• Accurate assignment of chorionicity:
Monochorionic.
• AFI
• Biometry and the percentile of GR
• Doppler waveform of FUA,MCA ,DV Flow
• Urinary Bladder
• In case of death of one fetus in utero there are
12% chances of Iufd of second twin.

51. Complications of MP
• Increased maternal morbidity
• Fetal and neonatal morbidity and mortality.
• Preeclampsia,
• Gestational diabetes
• Preterm labor and delivery
• Growth restriction/Discordant growth/fetal demise
• Cholestasis,
• Dermatoses,
• Excess weight gain,
• Anemia,
• Hyperemesis gravidarum,
• Exacerbation of pregnancy-associated gastrointestinal symptoms (reflux,
constipation) .
• Chronic back pain,
• Intermittent dyspnea,
• Postpartum laxity of the abdominal wall, and umbilical hernias also occur
frequently
• Perinatal morbidity and mortality associated with multiple gestations relates
directly to the consequences of preterm birth .

52. • 39yr female with secondary infertility.
• Conceived with FTET in second IVF Cycle.
• Triplets reduced to twins.
• c/o itching .Blood test reported as :
Total Se Bilirubin - 1.32mg/dl
Direct 0,77mg/dl
Indirect 0.55mg/dl
SGOT 62.69IU/L
SGPT 90.01IU/L
Alkaline phosphatase 1117.48U/L

53. • 30 yr F twins from donor eggs.
• 24 wks...B.P. 130/90 .RFT/LFT ...normal range.
• Comes at 26wks with :
• H/o Oliguria since 5-6 days,excessive oedema of
face and legs and feet since two days.Urine
output <200ml in 24 hrs.
• B.p.170/110.Blood work showed only low TSP
Low Albumin. 24 hr urinary proteins high.

54. • Role of Low dose aspirin and Heparin?
Risk of TED

55. Strategies to limit risks of multiple
births?

56. • eSET
• Limit the number of ET ,guiding factors being
maternal age,prognostic factors,quality of
embryos.
• Highly efficient cryopreservation protocols for IVF
Clinics.
• National registry for keeping record of all OI/SO in
order to assess actual proportion of twins
attributable to ART
• National health insurance schemes for ART
Procedures.

57. Factors affecting application of e SET
• 1.Desire to achieve higher preg per transfer
• 2.Selection of best embryo and best mother
• 3.Economic pressure on patients restricting
number of cycles taken
• 4.Good protocols for cryopreservation
• 5.Other socioeconomic,religious and cultural
factors

58. Double the giggles
Double the grins
Double the Trouble
When
You are blessed with twins