EARLY PREGNANCY CHALLENGES IN ART BY DR SHASHWAT JANI

1. Dr. Shashwat Jani.
M. S. ( Obs – Gyn ), F.I.A.O.G.
Diploma in Advance Laparoscopy.
Consultant Assistant Professor,
Smt. N.H.L. Municipal Medical College.
Sheth V. S. General Hospital , Ahmedabad.
Mobile : +91 99099 44160.
E-mail : drshashwatjani@gmail.com

2. • Management of pregnancies after IVF–ET
is difficult as the couples and treating doctors
have undue concern, apprehension, and worry
about outcome of such pregnancies.
• Patients are elderly and there may be
other co-morbid conditions; hence, pregnancy
after IVF–ET is considered as HIGH RISK.
17-Mar-20
Dr Shashwat Jani.
99099 44160.
2
I.V.F. Pregnancies Are
Increasing Worldwide !!

3. • ART in most cases leads to
successful delivery of healthy
singleton pregnancies.
• However, there are
complications of pregnancy that
may develop more frequently in
those conceived using IVF–ET.
17-Mar-20
Dr Shashwat Jani.
99099 44160.
3

4. Precautions To Be Taken
In IVF Pregnancy
• Most of the IVF patients become
exceedingly elated when the result of
their pregnancy test is positive as their
trails and hard work during the tough
period have culminated something
fruitful…..
17-Mar-20
Dr Shashwat Jani.
99099 44160.
4

5. All Pregnancies Following I.V.F. Are
High Risk Pregnancies
• Woman must be sensitive and careful not
to become complacent ..as road ahead is
difficult.
• All complications of pregnancy are more in
couple where female factor is dominant.
• It is pertinent to note that ICSI patient with
male factor USUALLY does not cause adverse
outcome.
17-Mar-20
Dr Shashwat Jani.
99099 44160.
5

6. Outcomes Associated with
“Untreated infertility”
• There is increasing evidence that
infertility or subfertility is an
INDEPENDENT RISK FACTOR for
Obstetrical complications and adverse
Perinatal outcomes, even without the
addition of ART (level II)
17-Mar-20
Dr Shashwat Jani.
99099 44160.
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7. In Australia the average age of women going
for IVF with her own eggs is 36 years.
In India no such data is available.
It is estimated that average age of Indian
mother following self IVF cycle is same that is
35-36 years , while for donor cycle it is 42 years.
17-Mar-20
Dr Shashwat Jani.
99099 44160.
7
It Is A Fact---mothers With I.V.F. Pregnancy
Are 5 Years Elder Than Women Who Conceive Naturally

8. First Trimester Is
Most Difficult
17-Mar-20
Dr Shashwat Jani.
99099 44160.
8

9. • A positive BHCG test corroborates pregnancy
• Still unsure about pregnancy location and
viability
• While most pregnancies result in a baby,
about 25 - 35% pregnancies fail to beyond 12 weeks.
• It holds true for all natural pregnancies, not just
IVF pregnancies after infertility.
• Always remember that older women, have a
higher risk of miscarriage as compared to younger
women.
17-Mar-20
Dr Shashwat Jani.
99099 44160.
9

10. IVF pregnancies require close monitoring
in the first months itself …
• To ensure that everything proceeds smoothly.
• Initially, serial blood tests are done every 3
days, to check if the HCG levels are doubling.
• Once the HCG level exceed 1000 mIU/ml, then
vaginal ultrasound are done to confirm that the
pregnancy is in the uterus and is growing well.
17-Mar-20
Dr Shashwat Jani.
99099 44160.
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11. Challenges in 1st Trimester :
 Multiple Gestation
 Bleeding in pregnancy / Miscarriage
 Ectopic Pregnancy
 Heterotopic pregnancy
 Hyperemesis
 Abnormal Placentation
 Psychological issues
 Birth Defects
 OHSS / Ovarian torsion
 Complications of Medical disorders related to
advance age
17-Mar-20
Dr Shashwat Jani.
99099 44160.
11

12. • EARLY PREGNANCY LOSS…
Due To Biochemical Pregnancy,
It Is Distinct & Different Entity As Compared
To First Trimester Miscarriage..
• ACCORDING TO W.H.O. & ESHRE
…ULTRASOUND EVIDENCE OF PREGNANCY IS
ESSENTIAL FOR COUNTING IT AS CLINICAL
PREGNANCY
17-Mar-20
Dr Shashwat Jani.
99099 44160.
12

13. Early Pregnancy Complications
• CLINICAL MISCARRIAGE RATE after I.V.F. = 10-15% attributed to
ADVANCED AGE,PCOD,OBESITY &OTHER COMORBIDITIES
• However, It is pertinent to note that the problem of Bleeding
is seen in more than 50% cases , more so in patients of PCOS.
• There is a positive correlation between the risk of abortions &
the intensity of ovarian stimulation.
• No difference in the miscarriage rates when comparing
couples who have had both fresh & frozen cycles unless PGD
testing is done.
17-Mar-20
Dr Shashwat Jani.
99099 44160.
13

14. Reasons for increased
Pregnancy loss are unclear!
Maternal age – esp over 40 years
Number of Embryos Transferred
Poor embryo quality at transfer
Luteal Phase Defect
Smoking
Associated Medical Conditions have been
shown to be associated.
17-Mar-20
Dr Shashwat Jani.
99099 44160.
14

15. It is interesting to note ……
• Frozen cycles babies have less problem
• ICSI does not increases rate of miscarriage,
adverse perinatal or maternal risk over standard
IVF.
• Use of donor oocytes fair much better than
self I.V.F. cycles.
17-Mar-20
Dr Shashwat Jani.
99099 44160.
15

16. Fact about Fresh v/s Frozen cycles
• There is growing evidence that pregnancy
outcomes are better for CRYOPRESERVED
EMBRYOS fertilized in vitro than for fresh
embryo transfers.
• This finding supports policy of freezing all
embryos in PCOS to give good prognosis , and
also reassures any women considering IVF (II-2A)
17-Mar-20
Dr Shashwat Jani.
99099 44160.
16

17. Overall 25 - 30% Of Women With Positive
Pregnancy Rate Will Lose Their
Pregnancy Before The End Of First Trimester if
not treated properly.
THE MISCARRIGE RATE
[Chemical Pregnancy Rate + Clinical Miscarriage
Rate]
= 20 – 30 %.
The High Loss Rate Highlights The Importance Of
Reporting Live Birth Following ART Rather Than
Pregnancy Rate…!!!
17-Mar-20
Dr Shashwat Jani.
99099 44160.
17

18. • Early vanishing twins (many being unrecognized)
following double-embryo transfer could be an
explanation for the increased incidence of first-
trimester bleeding in ART pregnancies.
• It is interesting to note that there is a linear
correlation between the incidence of first-trimester
bleeding and the number of embryos transferred.
• This is very suggestive of a vanishing twin effect.
• It has been shown that 10% of all singleton
pregnancies after IVF result from a vanishing twin
pregnancy (Pinborg et al., 2005).
17-Mar-20
Dr Shashwat Jani.
99099 44160.
18

19. Ectopic Pregnancy
Rate:
2 – 5%
Tubal factor: 11%,
Endometriosis: 2%
Unexplained infertility: 3.5%
IVF: 2.8%
ICSI: 1.3%
17-Mar-20
Dr Shashwat Jani.
99099 44160.
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20. Causes:
- The most significant risk factor :
Tubal pathology.
- Non significant factors:
Type of ovarian stimulation
E2 level
knee-chest or Lithotomy position at ET ,
Number of embryos transferred
According to Studies ,
Significantly lower ectopic pregnancy rate with
oocyte donation cycles
17-Mar-20
Dr Shashwat Jani.
99099 44160.
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21. It is interesting to note ……
• ICSI with IVF is associated with a significantly
lower risk of ectopic Pregnancy, because ICSI is
often selected for couples with male factor
infertility rather than tubal factor
• Oocyte donation (1.5%) and gestational
surrogacy (0.9%) have lower rates of ectopic
than IVF or the general population.
17-Mar-20
Dr Shashwat Jani.
99099 44160.
21

22. Possible Factors Associatedwith
Ectopic Pregnancy in IVF
Means of Prevention
Tubal disease, hydrosalpinx
Pre-IVF salpingectomy or tubal
occlusion
ET:
1. Depth
Mid-fundal transfer, ultrasound-
guided transfer (controversial)
2. Amount of mediaused 15–20 μL of media
3. Number of embryos
Reduced or single-embryo
transfer
4. Day 3 versus day 5
Controversial; some data suggest
fewer ectopics with day 5 transfer
17-Mar-20 Dr Shashwat Jani.
99099 44160. 22

23. Sites:
1. Tubal
2. Bilateral tubal
3. Intramural
4. Ovarian
5. Abdominal
6. Cervical {reflux of embryos into the
cervix after transfer or trauma to the
cervix during ET}.
17-Mar-20 Dr Shashwat Jani.
99099 44160. 23

24. Diagnosis:
• Highly sensitive ß-hCG assay & TVS
• The usual algorithms may not apply in ART {more
than one embryo usually is transferred, affecting ß-
hCG level}.
Marcus et al:
3ß-hCG levels& D13 progesterone combined with
a history of PID: predictive value of 90 %
Mol et al:
D9 ß-hCG, after ET of >18 IU/L: EP is only 1%:
expectant management (in an asymptomatic
patient)
17-Mar-20 Dr Shashwat Jani.
99099 44160.
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25. Prevention:
Prophylactic salpingectomy: Treat more than 89 %of
patients.
Disadvantages:
1. Removes any chance of normal spontaneous
pregnancy
2. Not prevent interstitial pregnancies.
17-Mar-20 Dr Shashwat Jani.
99099 44160.
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26. Heterotopic Pregnancy
Rate:
Spontaneous pregnancies: 1 in 2,600 to 1 in 30,000
ART: Recent reviews: 1-3 in 1000 pregnacies
% IVF Clinical
Pregnancies
% Spontaneous
Pregnancies
Ectopic pregnancy 2.2 1.3
Heterotopic pregnancy 0.5 0.07
17-Mar-20
Dr Shashwat Jani.
99099 44160.
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27. Cause:
Dr Shashwat Jani.
99099 44160.
 Multiple ovulations & multiple ET in a population
with tubal or pelvic disease.
Transfer of >4 embryos: increase risk.
 The technique of ET (volume& viscosity of
medium, deep or superficial insertion of the catheter,
and the degree of difficulty): inadequate data to draw
firm conclusions.
17-Mar-20 27

28. Risk
Delayed diagnosis: rupture, h'age
Diagnosis
TVS
Treatment:
1. Laparoscopic removal
2. TVS guided instillation of hyperosmolar glucose into
the ectopic gestational sac
3. Potassium chloride injection with aspiration of the
tubal sac
Dr Shashwat
Jani.
99099 44160.
17-Mar-20 28

29. Multiple Pregnancy
• There Is Epidemic Of Multiple Pregnancy With I.V.F.
• Multiple pregnancy is the MOST POWERFUL
PREDICTIVE FACTOR for adverse maternal,
obstetrical, and perinatal outcome.
• Couples should be thoroughly counseled about the
significant risks of multiple pregnancies associated
with ART.
• The figure is around 20%....
while in few earlier studies it crossed 40 to 50 %.
17-Mar-20
Dr Shashwat Jani.
99099 44160.
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30. Multiple Pregnancy
Dr Shashwat Jani.
99099 44160.
WHO recognized MP as a major complication of ART.
Rate:
In natural conception: 1 in 80 pregnancies
In ART: 1 in 50 , even in countries where the number of ET is
limited to 3 embryos.
In ESHRE report:
Singleton: 75.5%
Twin 23.2%,
Triplet 1.3%
Causes:
Ovulation stimulation drugs
17-Mar-20 30

31. Adverse outcomes:
1. Prematurity: short-term& long-term sequelae.
2. Neonatal mortality: 4 times as great among twins as it is
among singletons
3. Long-term disability e.g. cerebral palsy: increased.
4. Stress associated with rearing children
5. Cost of prenatal& neonatal intensive care: increased
IVF itself appears to increase
the risk of monozygous twins by two-fold
compared with natural conception,
17-Mar-20 31
Dr Shashwat Jani.
99099 44160.

32. Prevention:
ART success rate should be measured as a singleton live
birth rate & not as Pregnancy Rate.
1 Elective double ET :
Most European countries: reduced triplets & HOMP but
has had no impact on twin pregnancies
2 Elective single ET:
If significant risk of multiple gestation:
relatively young,
first or second IVF cycles, number
of good-quality embryos.
17-Mar-20 32
Dr Shashwat Jani.
99099 44160.

33. 3. Individualize protocols:
based on their risk of MP.
4-Multifetal pregnancy Reduction (MFPR)
Disadvantages
does not address the problem of twins.
ethical dilemma
psychological trauma
It should never be considered as a standard line for
prevention of MP and HOMP.
It is only a rescue if other methods fail in the prevention
17-Mar-20
Dr Shashwat Jani.
99099 44160.
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34. 5-Health education
of couples& the society on the hazards of MP&HOMP
6-Convince reproductive medicine physicians
-Obstetrical, neonatal, developmental & financial
consequences
-Measure of performance of ART is cumulative live birth per
patient not pregnancy rate per cycle
7-Convince policymakers consequences
of MP particularly cost
17-Mar-20
Dr Shashwat Jani.
99099 44160.
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35. Congenital Abnormality
Types
a. Major birth defects:
NTD, esophageal atresias, omphalocele, hypospadias, cardiac septal
defects
•Incidence
•little risk
•2 fold excess
•No higher rate of malformation in ICSI children than in IVF or
naturally conceived children (large and reliable surveys)
Explanation:
-Increased maternal age.
-During IVF: embryo is exposed to mechanical, thermal& chemical
alterations. Dr Shashwat
Jani.
99099 44160.
17-Mar-20 35

36. b. Chromosomal anomalies
Slightly increased in ICSI
Predominantly sex chromosomes
Dr Shashwat Jani.
99099 44160.
C. Imprinting Disorders
•Due to errors in imprinting, a process by
which certain genes from either the mother or
father are normally switched off.
17-Mar-20 36

37. Congenital Anomalies
Davies MJ et al., NEJM 201317-Mar-20
Dr Shashwat Jani.
99099 44160.
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38. 17-Mar-20
Dr Shashwat Jani.
99099 44160.
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39. Prevention
Dr Shashwat Jani.
99099 44160.
1. Proper genetic counseling of the couple
2. Karyotyping of male partners before
ICSI for severe oligoasthenospermia
or NOA.
3. Cystic fibrosis testing in both partners
before ICSI for CAVD
4. PGD in some patients
17-Mar-20 39

40. Abnormal Placentation
• Higher rates of placenta previa & abruption
are observed in IVF pregnancies compared to
non-IVF pregnancies.
• Frozen cycles are associated with decreased
risk of placenta previa and abruption .
17-Mar-20
Dr Shashwat Jani.
99099 44160.
40

41. Proposed Theory
• Metabolic changes in an embryo during
culture .
• Uterine stimulation causing contractility
during embryo transfer leading to increased
frequency of implantation in the lower segment .
• Recent study has suggested decreased
endometrial thickness during IVF is associated
with higher incidence of placenta previa.
17-Mar-20
Dr Shashwat Jani.
99099 44160.
41

42. Medical Conditions
• Increased medical complications in pregnancy
are noted in ALMOST 50% women who
conceived through IVF
• These include hypertensive disorders in
pregnancy , gestational diabetes.
• May be age-related/PCOD
17-Mar-20
Dr Shashwat Jani.
99099 44160.
42

43. Hyperemesis Gravideraum
• Morning Sickness
• Hyperemesis Gravideraum :
- Advance Age
- Medical Disorders like : Hypothyroidism …
- Supportive medications
- Psychological Anxiety.
17-Mar-20
Dr Shashwat Jani.
99099 44160.
43

44. • The venous thrombosis incidence is
significantly increased in pregnancies after in
vitro fertilization; especially in the first
trimester and in the first 6 weeks post-partum.
17-Mar-20
Dr Shashwat Jani.
99099 44160.
44

45. OHSS
• The incidence of OHSS varies between different
types of fertility treatment, with treatments
involving greater degrees of ovarian stimulation
being associated with a higher incidence.
• Following conventional IVF, mild OHSS has been
estimated to affect around one-third of cycles,
while
the combined incidence of moderate or severe
OHSS varies
from 3.1% to 8.0%
17-Mar-20
Dr Shashwat Jani.
99099 44160.
45

46. • Obstetric Complications:
MISCARRIAGE
PIH
PTL
VTE
Ovarian Torsion ( Surgical Emergency )
If conception occurs,
• Thromboprophylaxis should be continued
until at least the end of the first trimester.
17-Mar-20
Dr Shashwat Jani.
99099 44160.
46

47. Psychological Aspects
• IVF is a stressful event that influences women
during pregnancy, as evidenced by the
presence of high cortisol levels and anxiety
symptoms.
• Counseling , Counseling & Counseling.
• Tender Loving Care & Reassurance.
17-Mar-20
Dr Shashwat Jani.
99099 44160.
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48. To Summarize….
 While most assisted conceptions have a
normal course, not all do.
 The elective transfer of a single embryo
reduces many risks, but even singleton
pregnancies resulting from ART are at
increased risk of some maternal and fetal
complications.
17-Mar-20
Dr Shashwat Jani.
99099 44160.
48