art pregnancy complications prof. aboubakr elnashar
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ART PREGNANCY
COMPLICATIONS
Prof. Aboubakr Elnashar
Benha university hospital, Egypt
elnashar53@hotmail.com
Aboubakr Elnashar
Complications of ART I. COMPLICATIONS OF OVULATION INDUCTION
II. COMPLICATIONS OF OR
III. ART PREGNANCY COMPLICATIONS
IV. PSYCHOLOGICAL COMPLICATIONS
Aboubakr Elnashar
•At every stage of ART:
There is a potential for complications
some are dangerous& may be life threatening.
•Role of reproductive medicine clinicians:
1. Prevention of these complications
2. Establish the critical balance between efficacy and safety
of ART.
Aboubakr Elnashar
INCIDENCE •OHSS& OR complications: 1.3 %
•4 major clinical complications: 2%
Severe& moderate OHSS
Adnexal torsion
OR complications
Ectopic pregnancy.
Aboubakr Elnashar
All TT
cycles
First TT
cycle
Complication/1000
women
35 19 OHSS
2.5 1 Bleeding
11 5 Infection
93 42 Miscarriage
21 9.5 Ectopic
2 1 Other
5 2.5 Total
Aboubakr Elnashar
ART PREGNANCY
COMPLICATIONS
Aboubakr Elnashar
Maternal
I. First-trimester bleeding
II. Miscarriage
III.Ectopic Pregnancy
IV.Heterotopic Pregnancy
V. PIH, gestational DM, CS
VI.Placenta previa
VII.PTL
Foetal
I. Molar Pregnancy
II. Multiple Pregnancy
III. Congenital
Abnormality
Aboubakr Elnashar
A. Maternal I. First-trimester bleeding
Incidence:
29 -36.2%
Cause:
A correlation was found with the number of embryos
transferred.
Consequence:
1. Increased 2nd trimester& 3rd trimester bleeding
2. PROM
3. Preterm contractions & PTL
4. NICU admissions
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II. Miscarriage Rate: 15–23%
Causes: 1. Fertilization of postmature ova
2. Luteal phase defect
3. Adverse effects of handling the oocytes
4. False higher rate when compared to G population:
a. Different definitions of miscarriage,
b. Use of highly sensitive assays for b-hCG,
c. Close monitoring
d. knowledge that the embryos were transferred on a
particular day.
Aboubakr Elnashar
III. Ectopic Pregnancy Rate: 2 – 5%
Tubal factor: 11%,
Endometriosis: 2%
Unexplained infertility: 3.5%
IVF: 2.8%
ICSI:1.3%
Within the IVF group, EP was inversely correlated with
maternal age.
Aboubakr Elnashar
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
Aboubakr Elnashar
Possible Factors Associated with
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 media used 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
Aboubakr Elnashar
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}.
Aboubakr Elnashar
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)
Aboubakr Elnashar
Prevention: Prophylactic salpingectomy: Treat more than 89 %of
patients
Disadvantages:
1. Removes any chance of normal spontaneous
pregnancy
2. Not prevent interstitial pregnancies.
Aboubakr Elnashar
IV. Heterotopic Pregnancy Rate: Spontaneous pregnancies:1 in 2,600 to 1 in 30,000
ART: 1 in 100 pregnancies.
Recent reviews: 1-3 in 1000 pregnacies
% Spontaneous
Pregnancies
% IVF Clinical
Pregnancies
1.3 2.2 Ectopic pregnancy
0.07 0.5 Heterotopic pregnancy
Aboubakr Elnashar
Cause: 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.
Aboubakr Elnashar
Risk Delayed diagnosis: rupture, hage
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
Aboubakr Elnashar
V. PIH, gestational DM, CS •Are increased
PIH: IVF Vs Non IVF: (15 Vs 4%)
IUFD: 2%
•Reubinoff et al.
only found increased risk of: CS
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VI. Placenta previa Rate: 3-6 folds higher in singleton pregnancies compared with naturally
conceived pregnancies.
Cause: Women with pregnancies conceived after ART:
1. Older
2. More often primiparous.
3. More likely to have a multiple pregnancy.
Aboubakr Elnashar
VII. PTL PTL: Overall: 21.5-37% of births
Singletons: 5.5–13.0%
Low birth weight (<2,500 g): Overall: 30.5–37.5% all births
Singletons: 7.7–11.0%
Aboubakr Elnashar
B. Foetal I. Molar Pregnancy
Incidence:
Difficult to be assessed.
Causes:
1. Use of immature ova after ovulation induction
2. Disruption of meiosis& loss of maternal
chromosomes {oocyte handling or degeneration}:
increase the risk of complete mole.
3. Postmature oocytes are more prone to polyspermy: heterozygous complete or partial molar pregnancy.
Aboubakr Elnashar
Prevention: Modern molecular biology techniques
PGD
ICSI
Aboubakr Elnashar
II. Multiple Pregnancy 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 2006:
Singleton: 75.5%
Twin 23.2%,
Triplet 1.3%
Causes: Ovulation stimulation drugs
Aboubakr Elnashar
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
Aboubakr Elnashar
Prevention: ART success rate should be measured as a singleton
live birth rate& not as PR
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.
Aboubakr Elnashar
•ESET:
Reduces:
multiple pregnancy &
live birth in a fresh IVF cycle.
•<36 y
ESET
if needed, one frozen-and-thawed embryo
Reduces:
multiple births
live births: not substantially lower than the rate that is
achievable with a double ET.
Aboubakr Elnashar
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
Aboubakr Elnashar
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
Aboubakr Elnashar
III. Congenital Abnormality 1. General: 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.
Aboubakr Elnashar
b. Chromosomal anomalies Slightly increased in ICSI
Predominantly sex chromosomes
Aboubakr Elnashar
c. Imprinting disorders •Due to errors in imprinting, a process by which certain
genes from either the mother or father are normally
switched off.
•e.g.
Beckwith-Wiedemann syndrome (large tongue, organs,
and body size)
Angelman syndrome (a neurological disorder once
known as ‘‘happy puppet__ because of the child_s
sunny outlook and jerky movements).
•Evidence is suggestive but not sufficient
Aboubakr Elnashar
2. ICSI for patients with azoospermia {increased chromosomal aneuploidy rate}:
•Ludigs:
No additional risk of major malformations in children
testicular spermatozoa: 9%
ejaculated spermatozoa: 8.4%
Aboubakr Elnashar
3. Cryopreservation of embryos •{Cellular changes in cryopreservation& thawing}
•Rates of minor & major congenital malformation were normal, up to
the age of 4 ys
Aboubakr Elnashar
4. Vetrification Outcome of vitrified oocytes reported
fertilization rate: 92.9%
PR: 32.5
IR /embryo:13.2%
Babies born were healthy.
Aboubakr Elnashar
Prevention 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
Aboubakr Elnashar
IV. Stillbirth, perinatal mortality& infant
mortality •Higher {multiplicity& prematurity}..
•Case-control studies that account for confounding
variables do not always confirm this.
•IVF/ ICSI Twins
higher birth wt discordance
more NICU admissions
Aboubakr Elnashar
Recommendations: SOGC2014 Outcomes Associated with Untreated Infertility
infertility is an independent risk factor for obstetrical
complications and adverse perinatal outcomes, even
without the addition of ART. (II-2)
Aboubakr Elnashar
Outcomes Associated with Male Factor Infertility
All men with severe oligozoospermia or azoospermia
(sperm count <5 million/hpf) should be offered
genetic/clinical counselling,
karyotype assessment for chromosomal
abnormalities, and Y-chromosome microdeletion
testing prior to ICSI. (II-2A)
All men with unexplained obstructive azoospermia
should be offered genetic/clinical counseling and
genetic testing for cystic fibrosis prior to ICSI. (II-2A)
Aboubakr Elnashar
Obstetrical, Perinatal, and Long-Term Outcomes
Associated with ART
Multiple Pregnancy and Adverse Obstetrical and Perinatal
Outcomes
Multiple pregnancy is the most powerful predictive factor for
adverse maternal, obstetrical, and perinatal outcomes.
Couples should be thoroughly counselled about the significant
risks of multiple pregnancies associated with all assisted
human reproductive treatments. (II-2A)
The benefits and cumulative pregnancy rates of elective
single embryo transfer (eSET) support a policy of using this
protocol in couples with good prognosis for success, and
eSET should be strongly encouraged in this population. (II-
2A) To reduce the incidence of multiple pregnancy, health
care policies that support public funding for AHR, with
regulations promoting best practice regarding eSET, should
be strongly encouraged. (II-2A)
Aboubakr Elnashar
Singleton Pregnancies and Perinatal
Outcome/Preterm Birth/Low Birth Weight
Among singleton pregnancies, assisted reproductive
technology (ART) is associated with increased risks
of preterm birth and low birth weight infants, and
ovulation induction (OI) is associated with an
increased risk of low birth weight infants. Until
sufficient research has clarified the independent
roles of infertility and treatment for infertility, couples
should be counselled about the risks associated with
treatment. (II-2B) There is a role for closer obstetric
surveillance for women who conceive with AHR. (III-
L)
Aboubakr Elnashar
There is growing evidence that pregnancy outcomes
are better for cryopreserved embryos fertilized in
vitro than for FET. This finding supports a policy of
eSET for women with a good prognosis (with
subsequent use of cryopreserved embryos as
necessary), and may reassure women who are
considering IVF. (II-2A) Women and couples considering AHR and concerned about
perinatal outcomes in singleton pregnancies should be
advised that (1) ICSI does not appear to confer increased
adverse perinatal or maternal risk over standard IVF, and (2)
the use of donor oocytes increases successful pregnancy
rates in selected women, but even when accounting for
maternal age, can increase the risk of low birth weight and
preeclampsia. (II-2B)
Aboubakr Elnashar
Fetal Structural, Chromosomal, and Imprinting
Abnormalities Associated with Assisted Human
Reproduction
Structural Abnormalities (Malformations,
Deformations, and Disruptions)
Any ART procedure should be prefaced by a
discussion of fetal outcomes and the slight increase
in the risk of congenital structural abnormalities, with
emphasis on known confounding factors such as
infertility and body mass index. (II-2B)
In pregnancies achieved by ART, routine anatomic
ultrasound for congenital structural abnormalities is
recommended between 18 and 22 weeks. (II-2A)
Aboubakr Elnashar
Chromosomal Disorders
Pregnancies conceived by ISCI may be at increased
risk of chromosomal aberrations, including sex
chromosome abnormalities. Diagnostic testing
should be offered after appropriate counselling. (II-2A)
Imprinting Disorders
The relative risk for an imprinting phenotype such as
Silver-Russell syndrome, Beckwith-Wiedemann
syndrome, or Angelman syndrome is increased in
the assisted reproduction population, but the actual
risk for one of these phenotypes to occur in an
assisted pregnancy is estimated to be low, at less
than 1 in 5000. The exact biological etiology for this
imprinting risk increase is likely heterogeneous and
requires more research. (II-2) Aboubakr Elnashar
The possible increased risk for late onset cancer due
to gene dysregulation for tumour suppression
requires more long-term follow-up before the true
risk can be determined. (III-A)
Preimplantation Genetic Screening
The clinical application of preimplantation genetic
testing in fertile couples must balance the benefits of
avoiding disease transmission with the medical risks
and financial burden of IVF. (III-B)
Preimplantation screening for aneuploidy is
associated with inconsistent findings for improving
pregnancy outcomes. Any discussion of PGS with
patients should clarify that there is no adequate
information on the long-term effect of embryo single
cell biopsy. (I-C)
Aboubakr Elnashar
Guidelines for Reducing Complications of ART General Measures to reduce risk
1. BMI 2. Blood tests
3. Kidney function tests
4. Liver function tests
5. Blood sugar
6. FSH and E2
7. Abdominal and pelvic US
8. In selected patients:
ECG
Mammography
Salpingectomy
Hysteroscopy
Aboubakr Elnashar
Pregnancy complications 1. Uterine cavity empty with positive BHCC: exclude ectopic and
heterotopic pregnancies
2. Health education of patients on risks of MP
3. Single embryo transfer in selected patients
4. Multifetal pregnancy reduction for HOMP
Aboubakr Elnashar
Congenital of abnormalities 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
Aboubakr Elnashar
Thanks
Aboubakr Elnashar
Aboubakr Elnashar
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