1. Newer Modalities In The
Management Of Multiple Gestations
In Infertility Treatment
Moderator: Dr. Suman UG ma’am
Presenter: Dr. Sri Sushma Nagasuri
2. Introduction - Infertility
• Infertility is classically defined as the failure of a couple to conceive after 12 months of frequent
intercourse without use of contraception in women under age 35, and after six months in women over
age 35.
• The frequency of primary infertility in married women by age groups was
women 15 to 34 years (7.3 to 9.1 percent), 35 to 39 years (25 percent), 40 to 44 years (30 percent).
• One population-based study (Hull MG et al, Br Med J) showed the cause of infertility as:
• Male factor (hypogonadism, post-testicular defects, seminiferous tubule dysfunction) – 26 percent
• Ovulatory dysfunction – 21 percent
• Tubal damage – 14 percent
• Endometriosis – 6 percent
• Coital problems – 6 percent
• Cervical factor – 3 percent
• Unexplained – 28 percent
• Therapeutic interventions include reversing the cause, sex therapy, lifestyle modifications, and finally
assisted reproductive techniques.
3. Introduction - History
• The first pregnancy after in vitro fertilization (IVF) of a human egg and the first birth of an IVF
baby were reported in 1976 and 1978.
• Since then, an estimated 70,00,000 pregnancies have been achieved worldwide by IVF and its
modifications.
• These procedures are known generically as Assisted Reproductive Technology (ART) and include
• Ovulation Induction (with FSH and gonadotropin/ Chlomiphene)
• Intra Uterine Insemination (IUI)
• Oocyte transfer
• Intracytoplasmic sperm injection (ICSI)
• Gamete intrafallopian transfer (GIFT)
• Zygote intrafallopian transfer (ZIFT)
• Embryo transfer
4. Pregnancy outcomes in ART
• Conception by IVF is associated with an increased incidence of several obstetric and
perinatal complications including
• early loss,
• spontaneous abortion,
• ectopic pregnancy,
• preterm birth,
• Low Birth Weight (LBW),
• small for gestational age
• Most of these are related to the high incidence of multiple gestations [8].
• ART is also the the single biggest contributor to multiple pregnancy.
• Hence, the pregnancy outcomes in ART are more complicated than normal conception.
5. Comparison of selected pregnancy outcomes
after ART and natural conception
Hansen et al, N Engl J Med 2002; 346: 725
6. Impact of Multiple Gestation
• Multiple gestations are at significantly increased risk of fetal, neonatal, and
maternal complications, as well as complete pregnancy loss, when compared
with singleton pregnancies.
• As an example, in one review, the risk of delivery <32 weeks of gestation for
singleton, twin, triplet, and quadruplet pregnancies was 2, 8, 26, and >95
percent, respectively [8].
• In another study that compared twin pregnancy outcome with outcome of two
successive singleton pregnancies delivered by the same mother, adverse
pregnancy and neonatal outcomes were significantly increased for in vitro
fertilization (IVF) twins compared with two successive IVF singleton pregnancies
[9]
7. Incidence (%) of major maternal complications
in multiple pregnancies
8. Classification of multiple gestation
• Based on
• Zygosity (number of originating eggs/zygotes)
• Chorionicity (number of placentas) – more important
Mechanism of multiple gestation
• ART differs from normal pregnancy in that multiple embryos are
introduced into the uterus with higher chances of higher order
multiple pregnancy
14. Factors affecting multiple gestation risk
• Maternal age
• Embryo quality
• Number of eggs fertilized
• Morphology
• Preimplantation of genetic testing
• Assessment of non-invasive biomarkers
• Day of transfer
• Day 2 or 3 (cleavage stage)
• Day 5 or 6 (blastocyst stage)
15. Limiting the multiple gestation risk
• The contribution of ovulation induction to high order multiple births is rising, while the
number of these births from IVF is falling.
• Ovulation induction accounts for essentially 100 percent of multiple pregnancies with
six or more fetuses . Thus, ovulation induction and superovulation account for the
largest proportion of high order multiple gestations.
• The number of large follicles present on the day of human chorionic gonadotropin
(hCG) administration is a key factor in determining the risk of multiple gestation in
superovulation.
• Factors associated with the highest risk of high order multiple pregnancies included age
<32 years, having seven or more follicles of diameter ≥10 mm, and an estradiol
concentration ≥1000 pg/mL (note: this value is assay-dependent).
• In the first cycle, however, the dose of gonadotropin and length of stimulation are
highly important factors.
16. Strategies to reduce the high order multiple gestation rate from
ovulation induction
• Begin with medication regimens associated with a low incidence of
multiple follicles, including clomiphene citrate, aromatase inhibitors, and
pulsatile GnRH (where available), followed by the lowest effective
gonadotropin dose [8].
• Closely monitor follicle development with a strict cycle cancellation policy
for patients with an excessive number of mature follicles (eg, greater than
3 follicles ≥15 mm [103] or ≥16 mm [104]).
• Alternatives to cycle cancellation include aspiration of supernumerary
follicles before hCG administration or conversion to IVF.
• Pregnancy rates per patient would not be reduced if low gonadotropin
doses were continued for four to six cycles. As the majority of patients are
paying out of pocket for treatment, this might well be a difficult policy to
implement.
18. Types of fetal reduction
• Spontaneous fetal reduction (reabsorption)
• spontaneous death of one or more embryos
• Increased possibility before 11 weeks of gestation
• Multifetal pregnancy reduction (MFPR)
• Termination of one or more normal embryos in a higher- order multifetal
pregnancy
• Selective fetal reduction/Termination (ST)
• Termination of an abnormal fetus
19. Selective Termination
• A procedure in which one or more specific fetuses of a multifetal gestation are
terminated due to a confirmed or suspected abnormality that has been identified by
ultrasound examination or by definitive fetal diagnostic testing. These abnormalities
can include:
• chromosomal,
• structural,
• Genetic.
• ST avoids the live birth and long-term survival of a severely impaired child or a child
with lethal abnormalities. In some cases, termination of the anomalous twin may
optimize the outcome of the normal fetus.
• Loss rates after ST depend on starting and finishing numbers.
• In monochorionic fetuses, the most common method for ST is cord occlusion, because
it decreases the risk to the co-twin.
20. Multiple fetal reduction (MPR)
• MPR is a procedure in which the overall number of fetuses in the gestation is
reduced by terminating one or more fetuses mostly chosen randomly, but with
consideration of technical factors.
• The primary justification for MPR is that the "take home" baby rate per pregnancy is
increased by increasing the gestational age at birth and birth weight, thus reducing
morbidity and mortality from preterm birth (major benefit of MPR).
• The risks for some maternal complications, such as preeclampsia, are also reduced.
• Economic and psychological impacts of multiple gestation on families play a role.
• Risks associated and ethical issues related to it are still a debate.
• MPR is usually performed between 10+0 and 13+6 weeks of gestation but can be
performed later in gestation.
21. Multiple fetal reduction
• Prerequisites: Preprocedure chorionic villus sampling may be performed on the
fetus(es) that is not planned for reduction and does not increase postprocedural loss
rates while offering assurance of leaving behind a chromosomally normal fetus(es).
Sonographic assessment of fetal growth and development prior to the procedure is also
advised.
• The fetus(es) chosen for MPR is generally closest to the anterior uterine wall and/or the
fundus, as these sites are most accessible to transabdominal needle insertion. We inject
potassium chloride into the thorax, which causes asystole, but other drugs can be used.
• MFPR is usually carried out through transabdominal route with USG guidance.
• 2-3 Meq KCL is injected to each fetus that is to be terminated into fetal thorax, asystole
should be observed for 3 minutes
• Associated with 5-7 % risk of miscarriage.
• The maternal serum alpha-fetoprotein concentration is typically elevated for several
weeks after any fetal reduction procedure.
22. Historical techniques
• In the mid-1980s, transabdominal insertion of a needle,
manoeuvered into the fetal thorax for potassium chloride (KCl)
injection was described.
• Other techniques were mechanical fetus disruption, air embolisation
or electrocautery.
• In the 1980s and early 1990s, injection of sclerosing agents (such as
ethanol or cyanoacrylate-based sclerosants) or embolisation using
thrombogenic coils were described as being used to induce vascular
occlusion.
• Many newer and advanced modalities are now available.
23. • In the 1980s and early 1990s, vascular occlusion was induced by the
injection of sclerosing agents (such as ethanol or cyanoacrylate-based
sclerosants) or embolization using thrombogenic coils. However, these
techniques were associated with technical failure, so are no longer used.
• Modern vaso-occlusive techniques deliver focused heat to generate
occlusive coagulation of the umbilical cord or a large intrafetal vessel and
are performed as outpatient procedures under local anesthesia.
• Radiofrequency Ablation
• Bipolar diathermy cord coagulation
• Intrafetal laser ablation
• Suture ligation
Procedures for monochorionic fetuses
24. Radiofrequency ablation
• Timing: used between 15 and 27 weeks of gestation.
• Procedure: Using ultrasound guidance, a 17 G RFA needle is inserted
percutaneously at the level of the intrafetal portion of the umbilical cord.
Radiofrequency energy is applied at the electrodes (tines) situated on the
tip of the RFA needle, until an average temperature of 110°C is achieved in
all three tines for 3 minutes.
• Two or three such cycles may be applied until cessation of blood flow is
demonstrated by colour Doppler of the umbilical cord. RFA can be used in
MCDA pregnancies discordant for fetal anomaly
• if termination is not acceptable, then the alternative of fetoscopic laser
ablation of placental anastomoses can be offered.
• it is the procedure of choice for earlier MFPR of monochorionic embryos in
higher- order pregnancies (for instance, monochorionic triamniotic triplets)
and also for ST of the acardiac twin in twin reversed arterial perfusion
(TRAP) sequence
25. Bipolar diathermy cord coagulation
• Timing: between 18 and 27 weeks of gestation because there is an
increased risk of co-twin death at gestations earlier than 18 weeks.
• Following a small skin incision, and using ultrasound guidance, an
intra-amniotic 2.7 mm or 3.3 mm port is placed under local (or
regional) anaesthesia.
• Bipolar diathermy forceps (2.5 or 3 mm) are introduced to grasp a
free loop of the umbilical cord. The cord is fully coagulated along
several points using short bursts of 30–50 W bipolar electocautery for
up to 60 seconds per burst.
• The procedure is complete when colour Doppler shows cessation of
cord blood flow and fetal asystole.
26. Ultrasound-guided Suture ligation
• When: after 26 weeks of gestation
• Alternative procedure when the cord is too thick for bipolar
diathermy cord coagulation (BDCC) or RFA.
• A single port is inserted in the amniotic cavity and the looped end of a
monofilament suture is introduced using 2-mm forceps and placed
under the cord. The end of the suture is then grasped around the
cord and pulled out through the same port. Extracorporeal knot-tying
is applied using an endoloop pushing device, followed by
confirmation of cessation of cord flow using colour Doppler.
• This technique is now seldom used.
27. Intrafetal laser ablation
• A further alternative is the ultrasound-guided intrafetal ablation of
intra-abdominal aortopelvic vessels.
• An 18 G needle is inserted into the fetal abdomen, adjacent to the
pelvic vessels, then a 400-lm laser fibre is advanced 1–2 mm beyond
the tip of the needle. Laser coagulation is performed using an Nd:YAG
laser at 40 W until cessation of blood flow in the iliac arteries and
umbilical vein is demonstrated.
• Fetal asystole is confirmed around 60 minutes later.
• The advantage of intrafetal ablation is that it can be used when a free
loop of cord is not easily accessible, such as in TRAP sequence.
29. Indian Study 1
Selective fetal reduction in monochorionic twins: Preliminary experience
Vatsla Dadhwal,1,* Aparna K. Sharma,1 Dipika Deka,1 Latika Chawla,1 and Nutan Agarwal1
Author information Article notes Copyright and License information Disclaimer
1Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, New Delhi, India
* Address for Correspondence: E-mail:moc.liamtoh@dalstav
J Turk Ger Gynecol Assoc. 2019 Jun; 20(2): 79–83.
Published online 2019 May 28. doi: 10.4274/jtgga.galenos.2018.2018.0052
PMCID: PMC6558353
PMID: 30299263
Describes the experience of selective fetal reduction in complicated monochorionic twin pregnancies at a Maternal
Fetal Medicine unit in a tertiary care center in India.
30. Introduction
• In monochorionic twins, fetal reduction may be performed for indications other than twins
discordant for anomalies.
• Monochorionic twins have a unique set of complications such as twin-to-twin transfusion
syndrome (TTTS), selective fetal growth restriction, and twin reversed arterial perfusion sequence
(TRAP).
• These complications are due to the presence of inter-fetal vascular anastomoses, which may put
one twin at risk of death and adversely affect the health of the other twin. In the event of one
twin dying, the transfer of a significant amount of blood from the normal to the dying fetus,
through these placental vascular anastomoses, may occur leading to hypotension, hypo-perfusion
of the brain leading to cerebral injury (20-30%) and fetal demise (up to 10%)
• In a situation where death in one twin is imminent but pregnancy is very preterm, resorting to
fetal reduction can optimize outcomes in the surviving twin.
• Unlike dichorionic pregnancies, fetal reduction using potassium chloride (KCl) instillation in fetal
thorax/heart is not an option in mono-chorionic twins due to the presence of placental vascular
anastomosis; KCl might transfer to the other fetus and thus inadvertently cause demise of both
twins.
• Vaso-occlusive techniques such as bipolar cord coagulation (BPCC), radiofrequency ablation (RFA),
interstitial laser ablation (ILA) of cord, and fetoscopy-guided cord coagulation with laser are the
methods proposed for selective fetal reduction in complicated monochorionic twins.
31. Material and Methods
• This is a prospective study from June 2013 to June 2017
• Included 31 patients with complicated mono-chorionic twin pregnancies who underwent
selective fetal reduction.
• Informed written consent was obtained from each patient prior to the procedure.
Approved by the institutional ethics committee.
• Inclusion criteria: very preterm pregnancies with one fetus at risk of demise of and could
have adversely affected the other fetus. Methods used for cord coagulation were ILA,
BPCC, and RFA. ILA was used for fetal reduction in the first half of the study period,
whereas in the second half BPCC and RFA was used. The choice of method also
depended on the period of gestation and the indication for reduction.
• All procedures were performed under ultrasound (US) guidance, using aseptic
precautions. Patients received intravenous (i.v.) sedation, injection cefazolin (1 g i.v.) after
a sensitivity test, and one dose of 100 mg micronized progesterone intramuscularly (i.m.)
prior to the procedure as per the unit protocol. Trocar/needle insertion site was
infiltrated with 10 mL of 1% solution of xylocaine.
32. Results
• Technical success in 30/31 patients (98%)
• The mean gestational week at fetal reduction was 23 weeks and 2 days (range, 16-26+4 weeks).
• Early intrauterine fetal death (IUFD) occurred in 5/30 (16.67%) patients and late IUFD occurred in
1/30 (3.33%); there were 2 spontaneous abortions (6.66%).
• Both early and late fetal deaths happened in fetuses less than 24 weeks’ gestation. Thus, there
were 8 (26.67%) miscarriages (defined as pregnancy loss at or less than 24 weeks gestation).
• The mean gestational week at delivery was 35 (range, 26-39) weeks: 13/30 (43.33%) women
delivered at or beyond 36 weeks’ gestation, 2/30 (6.67%) delivered between ≥32-36 weeks, 3/30
(10%) delivered at ≥28-32 weeks’ gestation. Of the 4 patients who delivered between 24 and 28
weeks, 3 had stillbirths.
• The overall live birth rate was 19/30 (63.3%). There were 3 stillbirths (10%). These three patients
delivered between 26-28 weeks’ gestation.
• Vaginal birth was achieved in 18/30 (60%) patients. Four babies (21%) required care in the
neonatal intensive care unit.
34. Table 2: Perinatal outcome according to technique for selective fetal
reduction
35. Follow-up after the procedure
• We detected raised MCA PSV after the procedure in 3 cases, one of which
aborted subsequently. The other two pregnancies had a normal fetal MRI, the
values decreased on follow-up and they delivered a healthy baby at term.
• Fetal brain MRI was performed in 14 cases and was found to be normal.
• Patients were followed up bi-weekly for growth scans, and monitored for fetal
wellbeing. There was no evidence of infection (clinical) in the patients following
the procedures.
36. Discussion and conclusions
• On evaluation of perinatal outcomes after selective feticide in complicated
monochorionic twins. The overall survival rate of the co-twin was 63.3%. The survival
rate was lower with ILA (50%), whereas survival after RFA and BPCC was similar (71.4 and
75%).
• The authors observed that fetal survival rates were highest with RFA (86%), followed by
BPCC (82%), laser cord coagulation (72%), and lowest with cord ligation (70%).
• TTTS was the indication for reduction in 30% of cases.
• Survivors after selective feticide in monochorionic twins are at increased risk of
neurodevelopmental delay. Only few cases underwent MRI at follow up in our study.
• Fetal reduction procedures in monochorionic twins are considered to be considerably
complex and challenging.
• Data from initial cases of selective fetal reduction in complicated monochorionic twins
suggests that these procedures are feasible but are associated with high adverse
perinatal outcomes.
37. Indian Study 2
Radiofrequency Ablation in Complicated Monochorionic Pregnancy: Initial Experience
Shinde, R., James, P., Suresh, S. et al. J. Fetal Med. 5, 17–22 (2018).
https://doi.org/10.1007/s40556-017-0145-z
Mediscan Systems, No: 197, Dr Natesan Road, Mylapore, Chennai, Tamil Nadu, 600004,
India
Is a retrospective series of 15 cases of complicated monochorionic twin pregnancies
managed by RFA
One of the 3 studies published from India on this topic
Third study is a case study - Tayal T, Kaul A. Intrafetal laser ablation of umbilical vessels in acardiac twin with successful outcome. J Obstet
Gynaecol India. 2012;62(Suppl 1):43–5. [PMC free article] [PubMed] [Google Scholar]
38. Aims and objectives
• To evaluate outcomes of complicated monochorionic pregnancies
intervened by radiofrequency ablation (RFA) and report the initial
experience.
39. Material and methods
• Study design: retrospective case series
• Centre of study: Mediscan Systems Chennai, a tertiary referral Fetal
Medicine center
• Time frame: February 2015 till February 2017.
• Inclusion criteria: complicated monochorionic twin pregnancies
intervened by RFA
• Approved by the IEC
40. Results
• 15 cases were recruited.
• The procedure was technically successful in all cases.
• Main indication for RFA was sIUGR in 10 cases, of which 2 had
coexistent Twin to Twin Transfusion syndrome.
• Median gestational age at procedure was 22.6 weeks (IQR 21, 25.6).
• The median number of RFA cycles to attain cardiac asystole was 4
(IQR 3, 7).
• Four of the fifteen cases (27%) had procedure related complications
of which 3 occured within 2 weeks of procedure.
41. Follow up outcomes
• Perinatal outcomes were available for all 15 cases.
• There were 2 cases of preterm premature rupture of membranes which occurred
within 2 weeks of procedure.
• One case had a miscarriage within 2 weeks of procedure at 21 weeks, another
one had a mid-trimester loss 4 weeks after the procedure at 26 weeks.
• The median gestational age at delivery was 35 weeks (IQR 29.3, 35.5).
• Seventy-eight percent of the live borns were delivered after 34 weeks.
• The median procedure delivery interval was 10.4 weeks (IQR 4.1, 13.6). Median
birth weight at delivery was 2000 g (IQR 1300, 2600).
• The present series had a live birth rate of 87%. In this initial small series, there
was a good outcome in terms of live birth rates and ‘take home’ baby rates. The
efficacy needs to be ascertained by larger series and long-term neurological
outcome.
42. International Study 1
Intrafetal laser ablation for embryo reduction from dichorionic triplets to dichorionic
twins
Ultrasound Obstet Gynecol
2017 Nov;50(5):632-634.
doi: 10.1002/uog.18834. Epub 2017 Oct 5.
P Chaveeva 1 2, G Peeva 1, S G Pugliese 1, A Shterev 2, K H Nicolaides 1
Affiliations
1Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
2Dr Shterev Hospital, Sofia, Bulgaria.
43. Objective
• To report the outcome of dichorionic (DC) triplet pregnancies reduced
to DC twins by laser ablation of the pelvic vessels of one of the
monochorionic (MC) twins.
44. Methods
• Intrafetal laser embryo reduction (ER) from DC triplets to DC twins
was carried out in 61 pregnancies at 11 + 0 to 14 + 3 weeks’
gestation. Pregnancy outcome was examined.
45. Results
• Intrafetal laser was successfully carried out in all cases, but ultrasound
examination within 2 weeks of the procedure demonstrated that the MC
cotwin had died in 28 (45.9%) cases and was alive in the other 33 (54.1%).
• In the DC group, there was one miscarriage at 23 weeks, one neonatal
death after delivery at 26 weeks and in the other 31 cases there were two
live births at a median gestational age of 35.3 (range, 30.4–38.4) weeks.
• In the 28 cases in which both MC fetuses died, there was one miscarriage
at 16 weeks and in the other 27 cases the separate triplet was liveborn at a
median gestation of 38.2 (range, 32.2–42.1) weeks.
• The overall rate of miscarriage was 3.3% (2/61) and that of preterm birth
(PTB) at < 33 weeks was 6.8% (4/59).
46.
47. Conclusions
• In the management of DC triplet preg- nancies, ER to DC twins by
intrafetal laser ablation is associated with lower rates of miscarriage
or early PTB, compared with expectant management or ER by fetal
intracardiac injection of potassium chloride. How- ever, about half of
the pregnancies result in the birth of one rather than two babies.
48. International Study 2
Embryo Reduction in Dichorionic Triplets to Dichorionic Twins by Intrafetal Laser
Chaveeva P.a · Kosinski P.a · Birdir C.a · Orosz L.a · Nicolaides K.H.a, b
Harris Birthright Research Centre for Fetal Medicine
King's College Hospital
Denmark Hill, London SE5 9RS (UK)
E-Mail kypros@fetalmedicine.com
49. Objective
• To describe a new technique for embryo reduction (ER) in dichorionic
triplet (DCT) pregnancies.
50. Methods
• In 22 DCT pregnancies, ER to dichorionic twins was carried out at
11.3-13.9 weeks' gestation by ultrasound-guided laser ablation of the
pelvic vessels of one of the monochorionic twins.
51. Results
• Intrafetal laser was successfully carried out in all cases, but ultrasound
examination within 2 weeks of the procedure demonstrated that the
co-twin had died in 11 cases and was alive in the other 11. In the
dichorionic group there was one miscarriage at 23 weeks due to
cervical incompetence and in the other 10 cases there were two live
births at a median gestational age of 35.0 (range 32.2-37.1) weeks. In
the 11 cases where both monochorionic fetuses died the separate
triplet was live born at a median gestation of 38.0 (range 32.2-40.5)
weeks.
52.
53. Conclusions
• In the management of DCT pregnancies, ER to dichorionic twins by
intrafetal laser is an additional option to the traditional ones of
expectant management, ER by intrafetal injection of potassium
chloride (KCl) to monochorionic twins or ER by KCl to singleton.
