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

Avoiding Multiple Pregnancy in ICSI

By

Prof. Ahmed Abdel AzizChairman of Ob/Gyn

DepartmentAlexandria University

Overview

A multiple pregnancy is a pregnancy involving more than one fetus.

The largest multiple pregnancy on record led to the birth of nine offspring.

Overview

Twins are the most common type of multiple pregnancy.

The incidence of higher-order multiple pregnancies (triplets or greater) has increased >100-folds.

Births of single individuals (singletons) rose only 6% in that same time period.

Overview

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

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

Maternal risks and complications

Fetal Complications

Low birth weight wt <2500 gm is considered low, wt < 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 birth.

Fetal Complications

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

Overview

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 patients.

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 good.

Obstetrics & Gynecology 198871:289-296

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.

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 reduction;

(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 fetuses;

(c) post-fetal reduction: grieving for losing fetus, returning to the course of normal pregnancy.

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 17418207

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 mono-ovulation.

J Perinat Med. 2006 ;34 (5):355-8

Conclusion

1. High order multiple pregnancy has increased >100 folds due to IVF & COH.

2. It has many fetal and maternal complications.

3. Fetal reduction could be justified in these conditions.

Conclusion

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.

Conclusion

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 < 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 < 0.01).

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


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 (


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


Between June 2002 and December 2004, all patients (first cycle, female age <38 years) were offered the choice between having one (SET) or two (DET) embryos transferred.

Reprod Biomed Online. 2006 Sep ;13 (3):368-75


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.



The pregnancy rate following embryo transfer was significantly lower after SET compared with DET for both fresh (27.6 versus 36.9%; P < 0.05) and frozen-thawed (14.4 versus 23.5%) embryos.



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% )


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 sIVF.

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 importance.

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 transfer.

Reprod Biol Endocrinol. 2007 Jan 26;5 (1):2

The value of early cleavage (EC) is still being

debated.

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 (SET)

Reprod Biomed Online. 2007 Jan ;14 (1):85-91

The value of early cleavage (EC) is still being debated

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 < 0.05) and 42.4 versus 25.9% (P < 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 <36 years in their first treatment cycle to avoid multiple pregnancies

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.


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 pregnancy.


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

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


MET

CONCLUSION(S): Cautious patients, preferred transfer

of fewer embryos. 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.



MET

Providing risk information increased the desirability of elective single-embryo transfer and decreased the desirability of twin pregnancy among both men and women.


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

Conclusion

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

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

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