PREGNANCIES BY OVUM DONATION

Zeev Shoham, MD

Director of the Reproductive Medicine and IVF Unit

Department Ob/Gyn, Kaplan Medical Center

Rehovot , Israel

1.Premature ovarian failure 2.Poor responder 3.Menopause (surgical, radiotherapy, chemotherapy) 4.Advanced maternal age 5.Recurrent IVF failure 6.Poor oocyte quality 7.Genetic defects precluding normal pregnancy 8.Combined

Indications for egg donation

Ovum Donation

• Highest efficacy independent of age

• Highest efficacy independent of indication

• Proven safety

• Pragmatic solution

Cummulative pregnancy rates after

1, 2 and 3 attempts

Recipients

30-50 Years

OD: highest implantation rates in ART

(Cohen et al., 1999)

Delay in parenthood

Social revolution 60´s contraceptive pill

Female´s priorities:

Education and work

Divorces

New family models

TRENDS

• Recent decades have witnessed an increase in mean

maternal age at childbirth in most high-resourced

countries

• United States

• 1970- 1 out of 100 first births to women aged >35 years

• 2006 - 1 out of 12 first births to women aged >35 years

Martin et al. (2009) National Vital Statistics Reports

BIOLOGICAL CLOCK

Ovarian reserve

• The exact age at which a women can no longer conceive varies widely.

Females born with a finite pool of oocytes ( Zukerman 1951)

Live birth per transfer of fresh embryos from own and donor eggs, by age of

receopint.

HOW OLD?

Birth as old as 67 yrs. of age using ART have been reported.

(Unfortunately - 2 years later - cancer)

"Health | World's oldest mother dies at 69". BBC News. 2009-07-15. Retrieved 2012-11-08.

Oldest women to conceive naturally was 57 yrs. old.

"Oldest mother to conceive naturally". Guinnessworldrecords.com. 1997-08-20. Retrieved 2012-11-08.

Oocyte Donation

Only effective option for women over the age of 40 with

diminished ovarian function.

The risk of chromosomal abnormality correlates to the

age of the donor, but the risks of pregnancy complications

(DM, HTN) correlate to the recipient’s age.

Published by IVF-Spain

Types of gamete donation

• Altruistic donation

• Donation with payment to donor

• Sharing

• Reciprocal donation

Upcoming challenges, Leiderdorp, 04.10.2013 13

Pregnancies achieved using ED with unrelated donors are

unique, since the entire fetal genome is allogeneic to the mother.

• The first successful pregnancy achieved after egg

donation (ED) was reported in 1984 Lutjen et al. Nature 1984;307:174-175.

• The original indication was premature ovarian failure Bustillo et al. JAMA 1984;251:1171-1173.

1999 - Oocyte donation (USA) was performed in almost 10% of all ART

cycles carried out in US (CDC report, 1999)

2012 - Oocyte donation (USA) was performed in almost 12% of all ART

cycles carried out in US (CDC report, 2012)

Pregnancy rate

Delivery rate

One cycle 53.4% 42.6%

Four transfers 94.8 78.7%

Remohi et al. Fertil Steril. 1997;67:717-23.

What might be the medical

problem, related to pregnancy

from egg donation?

HYPERTENSION

The most frequent medical problem in pregnancy.

Older women have a two fold higher risk of being

diagnosed with HT.

Preeclampsia in general population is 3 to 4%. 5 to 10%

in women >40

Pecks et.al. Dtsch Arztebl Int.

Oocyte donation: a risk factor for pregnancy-induced hypertension: a meta-

analysis and case series.

28 publications were evaluated.

PIH in a total of 2308 deliveries after oocyte donation was 22.6%.

The calculated odds ratio for PIH after oocyte donation, compared to other women in the control group, was 6.60

(95% CI, 4.55-9.57).

• Am J Obstet Gynecol. 2014 Levron et al.

To determine the prevalence of placental complications in patients conceived through donor versus autologous oocytes.

The rate of placental complications including:

Preeclampsia

Gestational hypertension

Intra uterine growth restriction (IUGR)

A retrospective cohort study

Donor oocyte (n=139)

Autologous oocyte (n=126).

Only singleton gestations were included

Ovum donor recipients

Age: Older 45 vs 41, p<0.01

Gestational hypertension and preeclampsia 25% vs 10%, p<0.01

IUGR 9.3% vs 4%, p=0.08

Adjustment for maternal age, gravidity, parity and chronic hypertension revealed independently higher rate of hypertensive diseases of pregnancy (P=0.01).

• Am J Obstet Gynecol. 2014 Levron et al.

Bellver et al. Fertil Steril. 2013;100:1050

Obesity - uterine receptivity - ovum donation

Analyze the reproductive outcome of recipients of donated ova according BMI.

9,587 first cycles of ovum donation with ova from normoweight donors

Outcome was analyzed according to the BMI

BMI <20 kg/m(2) (n = 1,458; 15.2%)

Normo-weight with BMI 20-24.9 kg/m(2) (n = 5,706; 59.5%)

Overweight with BMI 25-29.9 kg/m(2) (n = 1,770; 18.5%)

Obese with BMI ≥30 kg/m(2) (n = 653; 6.8%).

Lean Normo-weigh Over-weight Obese

Implantation

40.4% 39.9% 38.5% 30.9%

Clinical pregnancy

56.9% 55.9% 54.3% 45.3%

Live-birth 38.6% 37.9% 34.9% 27.7%

Bellver et al. Fertil Steril. 2013;100:1050

Female obesity impairs the reproductive outcome of ovum donation probably as

a result of reduced uterine receptivity

Conclusions

• Pregnant woman who have conceived as a result of

oocyte donation are to be categorized as high risk

patients, with a substantial risk especially for hypertensive

disorders of pregnancy.

• The increased relative risk for hypertensive disorders of

pregnancy exists independently of the rate of multiple

pregnancies, maternal age, and the type of reproductive

treatment.

DIABETES

Prevalence increases with maternal age

Rates of pre-existing DM and gestational

DM increase 3-6 fold in women >40.

Incidence of gestational DM in general OB population is 3%.

~7-12% in women over age 40

~20% in women over age 50

Placental Problems

Abruptio placenta

Placenta previa

Nulliparous women >40 have a tenfold increased risk of

placenta previa compared to women 20-29 yrs. old.

Van der Hoorn et al. Hum Reprod Update 2010:16;704

Perinatal Morbidity

Advanced maternal age is responsible for a substantial

proportion of the increase in the rate of LBW babies and

preterm delivery in the last several years.

Van der Hoorn et al. Hum Reprod Update 2010:16;704

Dysfunctional Labor And Cesarean

Section

Women age >35 yrs. are more likely to be delivered by C-

section.

C-section rates in general population in U.S. are almost

30%

Rate is almost 50% in women age 40-45

Van der Hoorn et al. Hum Reprod Update 2010:16;704

MATERNAL MORTALITY

Risk of maternal mortality for women age 35-39 yrs. old is

more than twice that of women age 25-29 yrs. old.

(21 vs. 9/100,000 live births)

Risk for women over the age of 40 is 5 x higher

Van der Hoorn et al. Hum Reprod Update 2010:16;704

Shrim et al., J Perinat Med. 2010 Nov;38(6):645-50..

Complications of very advanced maternal age pregnancies ≥ 45 years with and without ED.

Preterm deliveries (OR 1.25)

Cesarean sections (OR 1.84)

Hypertension (OR 1.71)

Diabetes (OR 2.45).

Small for gestational age (OR 1.30)

High rates of respiratory distress syndrome (OR 1.66)

Neonatal intensive care admission (OR 1.40)

Perinatal/neonatal mortality (OR 1.83)

>50% cesarean section

Postpartum hemorrhage (OR 5.38)

Ethics

Argument in favor of egg donation:

Reproductive freedom – regardless of age or life expectancy

Argument against:

Natural limits to reproduction, the child and medical risks

Therefore:

For maternal safety: Age limit should be 55 y.o.

Transfer of a single embryo (strongly considered)

The age and the health of the partner should be considered

Controversial issue

Several psychological studies show no difference in development and

happiness perception between “natural”, “IVF’ and “ED” children

Anonymity protects children and donors against trauma in adolescence

Anonymity vs. non anonymity

ANONYMITY VS. NON ANNONYMITY

Countries promoting non- and anonymous donations

Germany,

Austria,

Switzerland,

Italy

Russia and

Eastern

Europe

Spain,

France,

Greece,

Cyprus

Arab

world,

Africa

UK, BeNeLux &

Scandinavia

USA Canada

Conclusion

Egg donation has the highest efficacy independent of age or indication

Patients that have conceived through oocyte donation should be

categorized as high risk patients

Age limit should be 55 y.o.

Singleton pregnancy

Anonymity protects children and donors against trauma in adolescence