Invited lecture by Dr Sujoy dasgupta in the Annual Conference of the "Academy of Clinical Embryologists" (ACE) held in October 2021 in "Hybrid mode" (Kolkata and Webinar)

1. Dr Sujoy Dasgupta
MBBS (Gold Medalist, Hons)
MS (OBGY- Gold Medalist)
DNB (New Delhi)
MRCOG (London)
Advanced ART Course for Clinicians (NUHS, Singapore)
Diploma, Sexual & Reproductive Medicine (South Wales, UK)
Consultant: Reproductive Medicine, Genome Fertility Centre, Kolkata
Visiting Consultant, RSV Hospital, Kolkata
Bhagirathi Neotia Women and Child Care centre
Woodlands Multispeciality Hospital, Kolkata
Managing Committee Member, Bengal Obstetric & Gynaecological Society (BOGS)
Executive Committee Member, Indian Fertility Society (IFS)- West Bengal Chapter
Executive Committee Member, Indian Society for Assisted Reproduction (ISAR)- Bengal
Winner, Prof Geoffrey Chamberlain Award, RCOG World Congress, London, 2019
Multifoetal reduction in Infertility

2. High order multiple pregnancy
(HOMP)
• Defined as presence of ≥3 fetuses in utero
• Maternal and fetal risks
• Prematurity- twin 60%, triplets 75%
• The chances of spontaneous loss of the entire
pregnancy is 25% for quadruplets, 15% for
triplets and 8% for twins.

3. ART and HOMP
• Can be significantly controlled following the
policy of single embryo transfer (SET).
• SET does NOT compromise the cumulative live
birth rate compared to double embryo transfer,
while sparing the risk of multiples.
• Similar trends have been noted in India too
• ART itself may induce monozygotic twinning
• Cancellation of hyperstimulated cycles
• Reducing dose of gonadotrophins
• Conversion to IVF if >3 follicles develop.

4. Multifetal Pregnancy Reduction
(MFPR)
• Technique to reduce the complications of HOMP by
converting them into twins or sometimes into
singletons
• outcome may be as good as unreduced twins
• can also reduce the risk of maternal complications
• Does not increase the risk of congenital anomaly for
the surviving fetuses.
• Does not appear to affect the long term development
of the baby expected for gestational age and birth
weight
• a lower-order pregnancy reduces the risk of
complications

5. Beriwal S, Impey L, Ioannou C. Multifetal pregnancy reduction and
selective termination. The Obstetrician & Gynaecologist
2020;22:284–92.

6. Methods of MFPR
Independent chorionicity
• Mechanical disruption
• Air embolisation
• Electrocautery
• Direct intracardiac injection
of KCL, as an outpatient
procedure under LA
Monochorionic
• Radiofrequency ablation
• Bipolar diathermy cord
coagulation
• Intrafetal laser ablation
• Suture ligation

7. Chorinicity
• Most important parameter determining the
outcome and management
• Should be clearly determined in early
pregnancy, preferably before 14 weeks
• Reduction of monochorionic (MC) pair in
HOMP is associated with much lower risk of
prematurity and better survival

8. Timing of MFPR
7-8 wk- vaginally
• Extreme obesity
• Thick abdominal scar
• When the lower fetus
cannot be approached
abdominally
• Risk of infection?
11-14 wk- abdominally
• Allows checking for gross
structural abnormalities in the
fetus.
• Allows enough time for
spontaneous reduction to
happen (>50% cases of HOMP
in the first trimester)
• Never >16 wk
• Some anomalies may not be
detected

9. Miscarriage
• Systematic review- risk of miscarriage is not
significantly increased by MFPR in triplets, 7.4%
for expectant management versus 8.1% for
reduction.
• The risk of miscarriage is probably higher- partly
attributed to the invasive nature of MFPR.
• A residual risk of pregnancy loss for several
weeks- the amount of dead fetoplacental tissue
present in utero.

10. Preterm Delivery
• Risk can at best be reduced, not eliminated (56%)
• Following reduction to DCDA twins from TCTA
triplets, the risk of birth before 33 weeks of
gestation is 13.1% compared with 35.1% with
conservative management.
• Data on prematurity for MFPR in quadruplets is
rather limited
• The median age of delivery in cases of live births
after MFPR was 36.9 weeks

11. Complications
• No increased risk of DIC
• Could decrease the risk of preeclampsia
• Groutz et al- high incidence of pregnancy-
induced hypertension in quadruplets reduced
to twin than nonreduced twins
• The risk of suboptimal outcome after MFPR
was more with the higher initial number of
fetuses

12. Ethical dilemma
• Making an informed choice in absence of any
identifiable severe fetal abnormality.
• Sacrificing apparently healthy fetus(es) in order to
prevent severe preterm birth of the remaining fetus(es)
• Pre-procedure sex selection
• Delayed diagnosis of anomaly in the remaining fetuses
• Reduction to singletone?
• 30–70% of women undergoing MFPR may experience
acute feelings of anxiety, stress and emotional trauma
• The parental distress declines over time
• The role of continued counselling

13. HOMP- NOT the primary aim
• Should not be viewed as an integral part of
the ART programme
• Not devoid of any obstetric complications.
• Primary prevention of multiple gestation is of
utmost importance.
• Reduction should be taken as the last resort

14. Literature
• Triplets
• Quaduplets-?

16. Case Series
• Quadruplet pregnancies referred to a single
fetal medicine unit (Institute of Fetal
Medicine, Kolkata)
• Over a period of two years from January 2018
to December 2019

17. Aims and Obsjectives
Primary objective
• The procedure-related
pregnancy loss- miscarriage
within 2 weeks of the
procedure.
• Overall pregnancy-loss
rate- pregnancy loss before
24 completed weeks of
gestation.
Secondary objective
• incidence of obstetric
complications and preterm
delivery, defined as delivery
before 37 completed weeks
of gestation.

18. Before the study
• Approved by the IEC of Institute of Fetal
Medicine, Kolkata.
• Thorough counselling in their first visit,
preferably before 10 weeks of gestation.
• Written information on risks and benefits of
continuing with quadruplets versus MFPR.
• Informed written consent

19. Procedure
• Detailed ultrasound scan
• 11 and 15 weeks of gestations
• Under strict aseptic precautions and using 1% lignocaine
• 20G spinal needle was advanced through the maternal lower
abdominal wall into the uterine cavity, to reach the targeted fetal
thorax under direct ultrasound guidance (Voluson E8, Curvilinear
transducer 2-9 MHz).
• 0.5-1.0 ml of 10% KCl was injected into the fetal heart from a
preloaded 2ml syringe taking particular care to avoid inadvertent
passage to the amniotic fluid of the neighbouring embryos.
• Fetal asystole was confirmed before withdrawing the spinal
needle
• Repeat ultrasound examination performed 30 minutes later.

20. Procedure (contd…)
• Separate needles and KCL syringe were used for
individual fetuses.
• Only one fetus was injected for the monochorionic
pairs.
• The fetuses with larger NT, smaller CRL or major
structural abnormality were selected for reduction.
• Otherwise the fetuses remaining closest to uterine
fundus and most accessible were selected.
• Antibiotic prophylaxis
• Anti-D immunoglobulin prophylaxis, if suitable.
• Emergency helpline number provided.

21. Results
• Total 20 women with quadruplets presented to our clinic.
• 4 conceived after OI and 16 after IVF.
• The mean (± SD) maternal age was 31.86 (±5.8) years
(range 24-43 years).
• 3 sets were trichorionic-quadriamniotic (TCQA),
• 17 were quadrichorionic-quadriamniotic (QCQA) type.
• All 20 women (100%) accepted MFPR after detailed
counselling.
• The mean (±SD) gestational age of MFPR- 11.9 (±0.94)
weeks (range 11-14.29 weeks).
• Success ratio of reduction (percentage of fetuses actually
reduced after attempt to reduce) was 100%.

22. Complications
• No pregnancy loss before 24 weeks.
• All but two women delivered before 37 weeks (four
PPROM, 13 preterm labour and one APH).
• Very high rate of preterm delivery at 90% (18/20).
• All (100%) were live births.
• Two cases of neonatal deaths where one baby died
from each set.
• All the women (100%) went home with at least one
baby.
• The mean birthweight (± SD) was 1729.34 (± 544.16)
grams (range 700-2600 grams)

23. Gestational age of delivery
24+0 and 27+6 wk 1 5%
28+0 and 30+6 wk 3 15%
31+0 and 34+6 wk 3 15%
35 and 36+6 wk 11 55%
≥37+0 wk 2 10%

24. Limitations
• Number of participants was also small.
• Long term follow up of the infants not done.

25. Conclusion
• Quadruplet pregnancies can happen despite all
preventive measures taken during fertility treatment.
• Timely referral to fetal medicine centre and adequate
counselling are important.
• Fetal reduction through abdominal route in late first
trimester can significantly reduce the risk of
pregnancy-complications.
• The risk of preterm delivery albeit reduced, remains
quite high.
• Finally, every attempt should be made for primary
prevention of HOMP.

26. References
• Murray SR, Stock SJ, Cowan S, Cooper ES, Norman JE. Spontaneous preterm birth prevention in
multiple pregnancy. The Obstetrician & Gynaecologist. 2018;20:57–63. DOI: 10.1111/tog.12460.
• National Institute for Health and Care Excellence (NICE) Guideline NG 137. Twin and triplet
pregnancy. 2019. Available at: https://www.nice.org.uk/guidance/ng137
• Beriwal S, Impey L, Ioannou C. Multifetal pregnancy reduction and selective termination. The
Obstetrician & Gynaecologist. 2020;22:284-92. https://doi.org/10.1111/tog.12690
• Evans MI, Berkowitz RL, Wapner RJ, Carpenter RJ, Goldberg JD, Ayoub MA, et al. Improvement in
outcomes of multifetal pregnancy reduction with increased experience. Am J Obstet Gynecol. 2001
Jan;184(2):97-103. doi: 10.1067/mob.2001.108074. PMID: 11174487.
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doi:10.1093/humrep/14.8.2170
• Mansour RT, Aboulghar MA, Serour GI, Sattar MA, Kamal A, Amin YM. Multifetal pregnancy
reduction: modification of the technique and analysis of the outcome. Fertil Steril. 1999
Feb;71(2):380-4. doi: 10.1016/s0015-0282(98)00461-0. PMID: 9988416.
• Benson CB, Doubilet PM, Acker D, Heffner LJ. Multifetal pregnancy reduction of both fetuses of a
monochorionic pair by intrathoracic potassium chloride injection of one fetus. J Ultrasound Med.
1998 Jul;17(7):447-9. doi: 10.7863/jum.1998.17.7.447. PMID: 9669303.
• Anthoulakis C, Dagklis T, Mamopoulos A, Athanasiadis A. Risks of miscarriage or preterm delivery in
trichorionic and dichorionic triplet pregnancies with embryo reduction versus expectant
management: a systematic review and meta-analysis. Hum Reprod. 2017 Jun 1;32(6):1351-1359.
doi: 10.1093/humrep/dex084. PMID: 28444191.