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Page 1: ART PREGNANCY COMPLICATIONS           Prof. Aboubakr Elnashar

ART PREGNANCY

COMPLICATIONS

Prof. Aboubakr Elnashar

Benha university hospital, Egypt

[email protected]

Aboubakr Elnashar

Page 2: ART PREGNANCY COMPLICATIONS           Prof. Aboubakr Elnashar

Complications of ART I. COMPLICATIONS OF OVULATION INDUCTION

II. COMPLICATIONS OF OR

III. ART PREGNANCY COMPLICATIONS

IV. PSYCHOLOGICAL COMPLICATIONS

Aboubakr Elnashar

Page 3: ART PREGNANCY COMPLICATIONS           Prof. 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.

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INCIDENCE •OHSS& OR complications: 1.3 %

•4 major clinical complications: 2%

Severe& moderate OHSS

Adnexal torsion

OR complications

Ectopic pregnancy.

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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

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Page 6: ART PREGNANCY COMPLICATIONS           Prof. Aboubakr Elnashar

ART PREGNANCY

COMPLICATIONS

Aboubakr Elnashar

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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

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Page 8: ART PREGNANCY COMPLICATIONS           Prof. 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

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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

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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

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Page 12: ART PREGNANCY COMPLICATIONS           Prof. 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

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Page 13: ART PREGNANCY COMPLICATIONS           Prof. 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

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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)

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Page 15: ART PREGNANCY COMPLICATIONS           Prof. 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.

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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

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Page 17: ART PREGNANCY COMPLICATIONS           Prof. 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.

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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

Page 19: ART PREGNANCY COMPLICATIONS           Prof. 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

Aboubakr Elnashar

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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.

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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

Page 22: ART PREGNANCY COMPLICATIONS           Prof. 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.

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Prevention: Modern molecular biology techniques

PGD

ICSI

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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

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Page 25: ART PREGNANCY COMPLICATIONS           Prof. 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

Page 26: ART PREGNANCY COMPLICATIONS           Prof. 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

Page 27: ART PREGNANCY COMPLICATIONS           Prof. 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

Page 28: ART PREGNANCY COMPLICATIONS           Prof. 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

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Page 29: ART PREGNANCY COMPLICATIONS           Prof. 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

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Page 30: ART PREGNANCY COMPLICATIONS           Prof. 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.

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Page 31: ART PREGNANCY COMPLICATIONS           Prof. Aboubakr Elnashar

b. Chromosomal anomalies Slightly increased in ICSI

Predominantly sex chromosomes

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Page 32: ART PREGNANCY COMPLICATIONS           Prof. 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

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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%

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3. Cryopreservation of embryos •{Cellular changes in cryopreservation& thawing}

•Rates of minor & major congenital malformation were normal, up to

the age of 4 ys

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4. Vetrification Outcome of vitrified oocytes reported

fertilization rate: 92.9%

PR: 32.5

IR /embryo:13.2%

Babies born were healthy.

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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

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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

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Page 38: ART PREGNANCY COMPLICATIONS           Prof. 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

Page 39: ART PREGNANCY COMPLICATIONS           Prof. 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

Page 40: ART PREGNANCY COMPLICATIONS           Prof. 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

Page 41: ART PREGNANCY COMPLICATIONS           Prof. 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

Page 42: ART PREGNANCY COMPLICATIONS           Prof. 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

Page 43: ART PREGNANCY COMPLICATIONS           Prof. 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

Page 44: ART PREGNANCY COMPLICATIONS           Prof. 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

Page 45: ART PREGNANCY COMPLICATIONS           Prof. 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

Page 46: ART PREGNANCY COMPLICATIONS           Prof. 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

Page 47: ART PREGNANCY COMPLICATIONS           Prof. 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

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Page 48: ART PREGNANCY COMPLICATIONS           Prof. 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

Page 49: ART PREGNANCY COMPLICATIONS           Prof. Aboubakr Elnashar

Thanks

Aboubakr Elnashar

Aboubakr Elnashar