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Avoiding Multiple Pregnancy in ICSI


Avoiding Multiple Pregnancy in ICSI By Prof. Ahmed Abdel Aziz Chairman of Ob/Gyn Department Alexandria University Single Embryo Transfer All of the SET patients, and ... – PowerPoint PPT presentation

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Title: Avoiding Multiple Pregnancy in ICSI

Avoiding Multiple Pregnancy in ICSI
  • By
  • Prof. Ahmed Abdel Aziz
  • Chairman of Ob/Gyn Department
  • Alexandria University

  • A multiple pregnancy is a pregnancy involving
    more than one fetus.
  • The largest multiple pregnancy on record led to
    the birth of nine offspring.

  • Twins are the most common type of multiple
  • The incidence of higher-order multiple
    pregnancies (triplets or greater) has increased
  • Births of single individuals (singletons) rose
    only 6 in that same time period.

  • The increase of multiple births is age related.
    According to the National Center for Health
    Statistics, over the last 20 years, multiple
    pregnancies in the United States have increased
  • 400 among women in their 30s and
  • 1000 in women in their 40s.
  • This trend is due in part to the fact that older
    women are less able to get pregnant naturally and
    are more likely to undergo infertility treatment


Maternal risks and complications
  • Miscarriages They are at least twice as common in
    multiple pregnancies.
  • Hyperemesis gravidarum
  • Pregnancy-induced high blood pressure
    Hypertension is 3 times more common in multiple
    pregnancies, and it is more severe.
  • Gestational diabetes .
  • Iron- and folate-deficiency anemias
  • It is generally recommended that women take
    60 - 80 mg of iron and 1 mg of folic acid
    supplementation daily to prevent anemia. A
    high-protein diet is also recommended.
  • Acute polyhydramnios occurs in about 5 - 8 of
    women who have a multiple pregnancy.
  • Vaginal and uterine hemorrhaging antepartum
  • Preterm labor and delivery
  • The average length of pregnancy is 39 weeks for
    singletons, 35 weeks for twins, 33 weeks for
    triplets, and 29 weeks for quadruplets.
  • Multiple pregnancy is, on average, 12 times more
    likely to be preterm. Prolonged hospitalization
    and surgical delivery

Fetal Complications
  • Low birth weight
  • wt lt2500 gm is considered low,
  • wt lt 1500 gm is considered very low.
  • Two-thirds of infants born from a multiple
    pregnancy are low birth weight and are at risk
    for significant short-term and long-term health
    problems as a result.

Fetal Complications
  • Birth defects Monozygotic twins are twice as
    likely as dizygotic twins to be born with
    congenital malformations .

Fetal Complications
  • Infant mortality can result from premature
    delivery in multiple pregnancy.
  • Most infant mortalities in preterm multiple
    deliveries occur in gestations less than 32 weeks
    and birth weights below 1500 gm.
  • Respiratory distress syndrome (RSD) accounts for
    50 of neonatal deaths resulting from premature

Fetal Complications
  • Cerebral palsy Infants born from a multiple
    pregnancy have a higher risk for cerebral palsy
    and other types of permanent neurological damage.

  • The financial, emotional and medical costs of
    multi-fetal pregnancies are extremely high.

Fetal Reduction
  • Fetal Reduction has been employed over the past
    two decades as a mechanism to reduce the
    morbidity and mortality of multiple pregnancies.
  • The procedure is successful in over 80 of

Selective Reductions
  • We argue that selective termination in
    appropriate circumstances (eg, when the ability
    to carry the pregnancy to viability is very
    small) is ethically justified because it meets
    the criterion of least harm and most potential

Obstetrics Gynecology 198871289-296
Fetal Reduction
  • There is technical, ethical, and psychosocial
    concerns about the proper use of multifetal
    pregnancy reduction

Fetal Reduction Types
  • Multifetal reduction is an outpatient procedure
    that is most successful when performed between 10
    and 12 weeks of gestation. It involves using
    ultrasound to guide the insertion of a needle
    through the abdomen to inject potassium chloride
    into one or more of the fetuses.
  • Multifetal reduction can be performed earlier in
    the pregnancy (between 6 and 8 weeks) using a
    transvaginal approach and embryo aspiration.
    There is a chance for spontaneous fetal reduction
    at this stage, and it is too early in the
    pregnancy to perform fetal screening for defects.

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Impact of fetal reduction on physical and
psychological well-being of women.
  • (a) pre-fetal reduction feeling threatened by
    the confirmed diagnosis of multifetal pregnancy,
    facing guilt and conflict of undergoing fetal
  • (b) undergoing fetal reduction getting confused
    due to family's concern about fetal reduction,
    losing a sense of body boundary intactness, and
    worrying about the safety of the remaining
  • (c) post-fetal reduction grieving for losing
    fetus, returning to the course of normal
  • The findings indicate that undergoing fetal
    reduction impacted the physical and psychological
    well-being of multifetal pregnant women.

Hu Li Za Zhi. 2006 Dec 53 (6)25-33 17160867
Fertil Steril. 2007 Apr 87 (4 Suppl 1)S44-6
Fetal Reduction
  • Success rates from fetal reduction have improved
    as a function of
  • increasing experience,
  • better ultrasound,
  • and lower starting numbers.
  • Genetic diagnosis prior to reduction can improve
    the overall outcomes.

Semin Perinatol. 2005 Oct 29 (5)321-9
Fetal Reduction
  • About 4-5 of women who undergo multifetal
    reduction miscarry the entire pregnancy as a
    result of the procedure.

Fetal Reduction
  • For all starting numbers, including twins,
    reduction to a lower number of fetuses
  • reduces fetal losses,
  • prematurity, and
  • infant mortality and morbidity.

Prenat Diagn. 2005 Sep 25 (9)807-13
Fetal Reduction
  • The use of chorionic villus sampling (CVS) before
    reduction has become a good practice to assure
    the likelihood of normal, remaining fetuses.

Evans. Reduction of Twins to a Singleton. Obstet
Gynecol 2004.
Non-selective Fetal reduction Is it a
Malpractice ?
  • From a medical point of view, this non
    evidence-based practice is not following good
    clinical practice.
  • multifetal pregnancies can be avoided by
    transferring only one or a maximum of two embryos
    by in vitro fertilization.
  • Further, ovarian stimulating programs should
    strictly adhere to protocols aiming at

J Perinat Med. 2006 34 (5)355-8
  • 1. High order multiple pregnancy has increased
    gt100 folds due to IVF COH.
  • 2. It has many fetal and maternal complications.
  • 3. Fetal reduction could be justified in these

  • 4. Fetal reduction is now safe and effctive in
    most of the cases.
  • 5. CVS before reduction is a good practice to
    assure normal remaining fetuses.

  • 6. Non selective fetal reduction could be
    considered a malpractice .
  • 7. Women receiving fetal reduction usually
    encounter difficult decision and tremendous
    emotional stress.

Single Embryo Transfer
  • To reduce the multiple pregnancy rate, eSET was
    introduced as a routine in patients with a high
    probability to become pregnant.

Single Embryo Transfer
  • In patients lt 36 years of age undergoing their
    first IVF-ICSI.
  • If two embryos showing satisfactory morphology
    are obtained, one is selected transferred and the
    other is systematically frozen.
  • Selection for transfer is based on two criteria,
    i.e. observation of even early cleavage 26 hours
    after IVF-ICSI and evaluation of embryo
    morphology score on day 2.
  • Embryo morphology score is based on the presence
    of four blastomeres and absence of blastomere
    irregularities and anucleated fragmentation.
  • Last, a prerequisite for SET is an effective
    freezing program.

Gynecol Obstet Fertil. 2006 Sep 34 (9)786-92
Single Embryo Transfer
  • A pregnancy rate of 13 per thawing was
    sufficient enough to obtain a cumulative
    pregnancy rate after SET (N 205) and subsequent
    frozen embryo transfer (FET) similar to the
    cumulative pregnancy rate obtained after double
    embryo transfer (N 394) and subsequent FET
    (46.3 vs 46.7, NS).
  • Twin delivery rate were respectively 2,6 after
    SET and 26,6 after double embryo transfer (P lt

Gynecol Obstet Fertil. 2006 Sep 34 (9)786-92
Single Embryo Transfer
  • In reports from Finland and Belgium already 5
    years ago, elective single embryo transfer (eSET)
    was shown to reach almost the same success rates
    as double embryo transfer (

Single Embryo Transfer
  • In both these Nordic countries around 60 of the
    transfers are today eSET and the multiple
    pregnancy rate below 10 with no triplets.

Single Embryo Transfer
  • Between June 2002 and December 2004, all patients
    (first cycle, female age lt38 years) were offered
    the choice between having one (SET) or two (DET)
    embryos transferred.

Reprod Biomed Online. 2006 Sep 13 (3)368-75
Single Embryo Transfer
  • All of the SET patients, and 82 of the DET
    group, had at least one embryo cryopreserved,
    (3.9 versus 2.8 embryos). The option of SET was
    continued for the frozen-thawed embryo transfers.

Reprod Biomed Online. 2006 Sep 13 (3)368-75
Single Embryo Transfer
  • The pregnancy rate following embryo transfer was
    significantly lower after SET compared with DET
    for both fresh (27.6 versus 36.9 P lt 0.05) and
    frozen-thawed (14.4 versus 23.5) embryos.

Reprod Biomed Online. 2006 Sep 13 (3)368-75
Single Embryo Transfer
  • However, the cumulative live birth rates
    following the transfer of fresh and frozen
    embryos were identical between the two groups (43
    versus 45), with a high prevalence of twins
    following DET (34 versus 0 )

Reprod Biomed Online. 2006 Sep 13 (3)368-75
Natural IVF
  • A total of 134 controlled natural IVF (nIVF)
    cycles were reviewed retrospectively and compared
    with 370 stimulated IVF (sIVF) cycles. The
    clinical pregnancy rate per embryo transfer
    following nIVF was 27 and 47 in sIVF cycles for
    patients aged less than 35.
  • However, natural cycle patients could attempt
    consecutive cycles with much less impact on their
    lives, both medically and financially.

Reprod Biomed Online. 2007 Mar 14 (3)356-9
Natural IVF
  • In patients under 35 years of age, the choice of
    controlled nIVF reduces the cost and risk to the
    patient, permitting her to have multiple,
    consecutive attempts, and cumulatively offers a
    clinical pregnancy rate which approaches that of

Reprod Biomed Online. 2007 Mar 14 (3)356-9
Embryo Selection
  • In IVF-ICSI cycles with single embryo transfer
    (SET), SELECTION OF EMBRYO is of crucial
  • The present study aimed to define which embryo
    parameters might be related to the implantation
    potential of advanced blastocysts.
  • CONCLUSIONS Developmental stage on day 5 and
    fragmentation rate on day 3 were related to the
    implantation potential of advanced blastocysts
    and should also be taken into account in the
    selection of the best advanced blastocyst for

Reprod Biol Endocrinol. 2007 Jan 265 (1)2
The value of early cleavage (EC) is still being
  • The aim of this prospective study was to examine
    the predictive value of EC assessment performed
    exactly 26 h after insemination by IVF or (ICSI)
    in a programme of elective single embryo transfer

Reprod Biomed Online. 2007 Jan 14 (1)85-91
The value of early cleavage (EC) is still being
  • Significantly higher overall clinical and ongoing
    pregnancy rates were obtained after transfer of
    an EC embryo than a non-EC embryo
  • 49.4 versus 33.3 (P lt 0.05) and
  • 42.4 versus 25.9 (P lt 0.02) respectively.

Reprod Biomed Online. 2007 Jan 14 (1)85-91
Preimplantation genetic diagnosis (PGD )
  • The Belgian legislation imposes single embryo
    transfer (SET) on women of lt36 years in their
    first treatment cycle to avoid multiple
  • The implementation of a SET policy in young women
    undergoing PGD for monogenic disorders and
    translocations enables a significant reduction of
    multiple pregnancies without significantly
    affecting the delivery rate.

Hum Reprod. 2007 Jan 4 17204531
Cost-effectiveness of SET Vs DET
  • The objective of this review is to determine
    which embryo-transfer policy is most
    cost-effective elective single-embryo transfer
    (eSET) or double-embryo transfer (DET)
  • A total of 496 titles were identified through
    the searches and resulted in the selection of one
    observational study and three randomized
    studies.. .(

Hum Reprod Update. 2006 Nov 10 17099208
Cost-effectiveness of SET Vs DET
  • DET is also most effective if performed in one
    fresh cycle
  • eSET is effective only when performed in good
    prognosis patients and when frozen/thawed cycles
    are included.

Hum Reprod Update. 2006 Nov 10 17099208
Cost-effectiveness of SET Vs DET
  • If frozen/thawed cycles are excluded, the choice
    between eSET and DET depends on how much society
    is willing to pay for one extra successful

Hum Reprod Update. 2006 Nov 10 17099208
Optimal time for selecting a single embryo for
transfer day3 Vs day 5.
  • To determine the best day for the selection and
    transfer of a single embryo, a prospective,
    randomized study was undertaken that compared the
    ongoing pregnancy rate (PR) after
  • single embryo transfer (SET) on day 3 with that
    after single blastocyst transfer (SBT) on day 5.
  • Results showed an overall significantly higher PR
    after SBT (32.8) compared with SET (23.2), and
    a PR of 40.8 after SBT versus 25.6 after
    excellent-quality embryos became available.

Fertil Steril. 2007 Feb 7 17292362 Nicolas H
Zech et al
Factors affecting patients attitude towards SET
and MET
  • OBJECTIVE To identify factors that influence
    patient decision making concerning embryo
  • DESIGN Prospective analysis.
  • SETTING In vitro fertilization unit at a
    tertiary-care, university-affiliated teaching

Fertil Steril. 2006 Nov 9 17097648
Factors affecting patients attitude towards SET
and MET
  • PATIENT(S) 79 women and 53 men who were referred
    consecutively for IVF treatment.
  • INTERVENTION(S) Provision of risk information
    about complications of twin pregnancy.
  • MAIN OUTCOME MEASURE(S) Rated desirability of
    different transfer options and twin pregnancy,
    together with standardized measures of depression
    and infertility stress.

Fertil Steril. 2006 Nov 9 17097648
Factors affecting patients attitude towards SET
and MET
  • Cautious patients, preferred transfer of fewer
  • Less-cautious patients may be motivated by
    beliefs about the influence of age, desires for,
    and likelihood of twin pregnancy.
  • Information about risks may affect these groups
    differently and
  • This may require good information to ensure
    informed consent.

Fertil Steril. 2006 Nov 9 17097648
Factors affecting patients attitude towards SET
and MET
  • Providing risk information increased the
    desirability of elective single-embryo transfer
    and decreased the desirability of twin pregnancy
    among both men and women.

Fertil Steril. 2006 Nov 9 17097648
Cochrane Review
  • Single embryo transfer significantly reduces the
    risk of multiple pregnancy, but also decreases
    the chance of live birth in a fresh IVF cycle.
  • Subsequent replacement of a single frozen embryo
    achieves a live birth rate comparable with double
    embryo transfer.

Hum Reprod. 2005 Oct 20 (10)2681-7
  • SET with maintenance of acceptable pregnancy
    rates can only be achieved if tools to select
    normal embryos are at hand(improved morphological
    criteria, biomarkers and PGD)
  • together with improved cryopreservation

Gynecol Obstet Fertil. 2006 Sep 34 (9)786-92

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Is e-SET a cost-effective alternative to DET ?
  • A review of the literature showed only five
    studies assessing both costs and consequences of
    strategies involving eSET compared with double
    embryo transfer.
  • Several limitations in these studies prevent a
    definitive conclusion on the cost-effectiveness
    of eSET being reached.

BJOG. 2006 Nov 2 17081184
  • INTRODUCTION In several clinics, elective
    single-embryo transfer (eSET) is applied in a
    selected group of patients based on age and the
    availability of a good-quality embryo. Whether or
    not eSET can be applied irrespective of the
    presence of a good-quality embryo in the first
    cycle, to further reduce the twin pregnancy rate,
    remains to be elucidated.

Hum Reprod. 2007 Apr 7 17416915
  • METHODS In patients lt38 years two transfer
    strategies were compared, which differed in the
    first cycle only
  • group A (n 141) received eSET irrespective of
    the availability of a good-quality embryo, and
  • group B (n 174) received eSET when a
    good-quality embryo was available while otherwise
    they received double embryo transfer (DET
    referred to as eSET/DET transfer policy).
  • In any subsequent cycle, in both groups the
    eSET/DET transfer policy was applied.

Hum Reprod. 2007 Apr 7 17416915
  • RESULTS After completion of their IVF treatment
    (including a maximum of three fresh cycles and
    the transfer of frozen-thawed embryos),
    comparable cumulative live birth rates (62.4 in
    group A and 62.6 in group B) and twin pregnancy
    rates (10.1 versus 13.4) were found.

Hum Reprod. 2007 Apr 7 17416915
  • CONCLUSIONS The transfer of one embryo in the
    first cycle, irrespective of the availablity of a
    good-quality embryo, in all patients lt38 years,
    is not an effective transfer policy for reducing
    the overall twin pregnancy rate.

Hum Reprod. 2007 Apr 7 17416915
Prefences of Subfertile women regarding e-SET
  • Additional IVF cycles are acceptablble ,
  • Lower pregnancy rates are not.
  • If elective single ET lowers pregnancy chances
    with 1, 3, or 5, the percentage of women
    preferring elective single ET drops to 34, 24,
    and 15, respectively.
  • If four, five, or six cycles with elective single
    ET are needed to match the success rate of three
    cycles with double ET, the percentage of women
    with a preference for elective single ET drops
    from 46 to 40, 36, and 35 respectively.

Fertil Steril. 2007 Apr 6 17416363
Prefences of Subfertile women regarding e-SET
  • With identical pregnancy rates after elective
    single embryo transfer (ET) and double ET
    strategies consisting of three cycles of IVF or
    intracytoplasmic sperm injection (ICSI) plus
    transfers of thawed/frozen embryos if available,
    46 of the women undergoing IVF/ICSI favor
    elective single ET.

Fertil Steril. 2007 Apr 6 17416363
Embryo Selection
  • METHODS Overall, in 203 cycles with SET,
    developmental characteristics of 93 implanted
    (group A) and 110 non-implanted (group B)
    advanced blastocysts of good quality were
  • The following developmental parameters were
    assessed in the two groups normal fertilization,
    developmental stage on day 5, number of
    blastomeres on day 2 and on day 3, fragmentation
    rate on day 3, compaction on day 4 and cleavage
    pattern on day 2 and day 3.

Reprod Biol Endocrinol. 2007 Jan 265 (1)2
Embryo Selection
  • RESULTS Expanded blastocysts compared to full
    blastocysts have higher implantation potential
    (56.5 vs. 29.3, plt0.05). In group B, a higher
    proportion of advanced blastocysts showed between
    10 and 50 anucleated fragments on day 3 than in
    group A

preimplantation genetic diagnosis (PGD)
  • METHODS A retrospective analysis of PGD cycles
    for monogenic disorders and translocations in
    women lt36 years on their first treatment cycle
  • .RESULTSThere was no significant difference in
    the delivery rates between the DET and the SET
    groups (33.9 versus 27.4, respectively).
    Multiple pregnancies were avoided when SET was
    performed. When monogenic disorders and
    chromosomal translocations were separately
    evaluated, no significant difference in the
    delivery rate after SET was observed.

Hum Reprod. 2007 Jan 4 17204531
Twin-to-singleton reduction ?
  • Until recently, multifetal pregnancy reductions
    to a singleton were rare.
  • Physicians had doubts about the justification to
    go "below twins."
  • However, physicians know that spontaneous twin
    pregnancy losses average 810.
  • Also, with experience, multifetal pregnancy
    reduction has become very safe.
  • Data suggest that the likelihood of taking home a
    baby is higher after reduction than remaining
    with twins.
  • We propose that twin-to-singleton reductions
    might be considered with appropriate constraints
    and safeguards.

Obstet Gynecol. 2004 Jul104(1)102-9 .
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