Paternal agePaternal age

Outcome of ICSIOutcome of ICSI

IntroductionIntroduction

• Life expectancy is increasing and is associated with changing patterns of marriage and divorce, so that remarriage and the wish to father a child in a new relationship are becoming increasingly common at an older age (Kühnert and Nieschlag, 2004).

EvidenceEvidence

• In the United States, there has been a 16% increase in the birth rate for fathers over the age of 35 (Ventura et al., 1997).

??? ART??? ART

• It is important to know whether advanced paternal age is associated with low outcome of assisted reproduction

Insufficient evidenceInsufficient evidence

• Contrary to the large number of studies which correlate maternal age with pregnancy rate in ART, there are few studies which reported relation of paternal age with fertilization and pregnancy rates in assisted reproduction.

• A major difficulty for the study of the relationship between paternal age and outcome of ART is the difficulty in controlling for age of women in two groups with a large difference in the age of men

AimAim

• is to study the effect of paternal age on the outcome of ICSI.

Inclusion criteriaInclusion criteria • male partners were 50 years of age

or more • first ICSI cycle• long agonist down-regulation

protocol. • subdivided into Group AI with their

age ranging from 50-59 years and • group A2 with their age of ≥ 60 .

Exclusion criteriaExclusion criteria

• female partners more than 40 years old

• azoospermia

ControlControl

• with paternal age below 50 years • with maternal age which matched

maternal age in Group A.

primary outcomeprimary outcome

• Fertilization rates• clinical pregnancy rates

InterventionsInterventions

• Ovarian stimulation, ICSI and Embryo transfer were done as described before (Mansour et al, 1996)usual

ResultsResults

Characteristic Group A Older men(n = 227)

Group B Younger men

(n = 227)

P-value

Paternal age (years) 53.9 ± 5.0 38.4 ± 5.8 <0.0001

Maternal age (years) 33.2 ± 4.9 32.7 ± 4.8 NS

Duration of infertility (years)

7.8 ± 6.2 7.8 ± 5.4 NS

Aetiology n (%)

Male factor 119 (52.4) 88 (38.8) 0.0047

Unexplained infertility 41 (18.1) 47 (20.7) NS

Tubal factor 28 (12.3) 46 (20.3) 0.031

Mixed 25 (11.0) 32 (14.1) NS

Ovulatory factor 14 (6.2) 14 (6.2) NS

Semen QualitySemen Quality

Characteristic Group A Older men(n = 227)

Group B Younger men

(n = 227)

P-value

Sperm concentration (×106/ml)

39.0 ± 26.3 46.0 ± 32.6 0.05

Sperm motility (%) 37.4 ± 20.4 46.4 ± 15.5 <0.0001

Sperm abnormal forms (%)

74.0 ± 11.5 81.3 ± 10.6 0.019

primary outcomeprimary outcome• The fertilization rate was significantly

higher in group B compared with group A (P < 0.0001;

• There was no significant difference between the number of grade I embryos in group A and group B

• There was no significant difference in clinical pregnancy rate between group A and group B (OR = 1.06, 95% CI = 0.72−1.55)

Outcome of intracytoplasmicOutcome of intracytoplasmic sperm injection cycles sperm injection cycles in Group A (male age ≥50 years) and Group B in Group A (male age ≥50 years) and Group B

(male age <50 years).(male age <50 years). Outcome Group A (n = 227) Group B (n = 227)

No. of oocytes 10.8 ± 6.8 10.5 ± 6.2

No. oocytes with polar body 7.9 ± 5.3 8.1 ± 4.9

No. 2PN embryos 5.1 ± 3.8 5.4 ± 3.5

Fertilization rate (%) 64.9 ± 25.4a 66.7 ± 25.6b

Grade of embryo 0.6 ± 1.1 0.7 ± 1.0

No. of cryopreserved embryos 1.9 ± 3.3 1.7 ± 2.8

No. of embryos transferred 2.7 ± 1.1 2.8 ± 1.0

Pregnancy rate (%) 37.9 36.6

a,bP<0.0001. There were no other statistically significant differences.

Subgroup analysisSubgroup analysis

Parameter Group A1 (n = 198) Group A2 (n = 29)

Paternal age (years) 52.5 ± 2.7 64.1 ± 6.2

Maternal age (years) 33.2 ± 4.9 33.5 ± 4.8

Duration of infertility (years) 8.0 ± 6.3 6.7 ± 5.7

No. of oocytes 10.9 ± 6.8 9.7 ± 6.3

No. of oocytes with polar body 8.0 ± 5.3 7.1 ± 5.1

No. 2PN embryos 5.2 ± 3.9 4.6 ± 3.5

No. of cryopreserved embryos 1.9 ± 3.3 1.7 ± 2.7

No. of embryos transferred 2.7 ± 1.1 2.5 ± 1.2

Pregnancy rate (%) 38.2 35.2

There were no statistically significant differences between the two groups

Multiple logistic regression analysis for Multiple logistic regression analysis for factors affecting pregnancy ratefactors affecting pregnancy rate

Factor P-value

Male age 0.6507

Female age 0.6356

Duration of infertility 0.8428

No. of oocytes 0.0079

No. oocytes with polar body 0.0056

No. 2PN embryos 0.8628

No. of cryopreserved embryos 0.6374

No. of embryos transferred 0.9361

• Several publications support the present data in suggesting that pregnancy outcome after ICSI is not affected by male age (Gallardo et al., 1996; Spandrofer et al., 1998).

HoweverHowever• This is the first study to report the

effect of different paternal age groups on the outcome of ICSI where maternal age was not significantly different between all groups and subgroups.

• The motility of spermatozoa in group B was significantly higher than group A (P < 0.0001); however, this is probably irrelevant, as ICSI was used in all patients.

Fertilisation rateFertilisation rate• In an egg donation programme, it

was found that age (up to 64 years) does not affect sperm characteristics or the ability of spermatozoa to fertilize human eggs. Embryo development in vitro, as well as implantation in recipient uteri, were not affected by the age of the male providing the semen sample.

• On the other hand, epidemiological studies have shown reduced fertilization potential with age in humans (Schwartz and Mayeaux, 1982; Mehken et al., 1986).

In our studyIn our study• The higher fertilization rate in group

(B) was not shown to affect pregnancy rate; one possible reason is that a much larger sample size would be required to show a difference in pregnancy rate

ConclusionConclusion• it seems that increased paternal age,

apart from its effect on lower fertilization rate, has no effect on pregnancy rate.

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