How does age affect IVF success rates ?

Pregnancy and live birth rates following ART decline with increasing age. Based on SART data.

Alviggi et al. Reproductive Biology and Endocrinology 2009 7:101   doi:10.1186/1477-7827-7-101

The woman’s age is the most important prognostic factor which determines IVF success. In sharp contrast, the age of the man doesn’t have a significant impact on the outcome of an IVF cycle. Pregnancy and live birth rate after IVF decline with increasing maternal age because the success of an IVF cycle depends on the number of eggs that can be harvested from the ovaries and their genetic quality.   As a woman ages,  her ovaries age too and old ovaries have poor ovarian reserve. Ovarian reserve is defined by the number of usable eggs left in the ovaries. 

Aging cause two significant changes in a woman’s ovaries :

1. The number of eggs present in her ovaries decreases  ( All the eggs that are present in a woman’s ovaries are formed when she was a fetus. Ovaries do not have the ability to produce new eggs and hence we do not know how to renew egg supply once this is exhausted !)
2. The quality of eggs (their genetic competence and mitochondrial quality ) remaining in her ovaries becomes poor too.

As a result, women of Advanced Maternal Age (AMA) have a poor chance of success with ART treatments. Even if they achieve a pregnancy, the chance of miscarriage is greater than 50% for women who are above 40 years old as compared to the miscarriage rate of 12% for women of 20 years. This high miscarriage rate is due to the presence of chromosomal abnormalities in older eggs. Eggs from older women have higher rates of anueploidy (the presence of wrong number of chromosomes ) and hence the embryos formed from such eggs are genetically incompetent . They often fail to implant ; and even if they do implant, they fail to give rise to a live, healthy infant.

After the age of 40, women have about a 10 % chance of conceiving per IVF cycle ; and even if they do the chance of miscarriage is as high as 50-80 %.  When an older woman uses eggs form a young woman (donated eggs), her chance of conceiving and having a successful pregnancy is as high as that of the young woman ! This indicates that the implantation and developmental potential of an embryo depends mainly on the age of the oocyte , and not on the age of the uterus ! This is why surrogacy is not usually be a reasonable solution for failed IVFs – most of the time the embryos do not implant because of a problem with the embryos (because of genetically incompetent eggs !) and not because of an incompetent uterus.

Read more at : http://www.drmalpani.com/infertilityintheolderwoman.htm

A comparison of CCRM's publication about blastocyst tranfer and blastocyst transfer after Comprehensive Chromosome Screening - are they biased?

I found two different publications of CCRM, one from the year 2000 and it talks about the importance of blastocyst transfer over day 3 embryo transfer. The other publication is a very recent one (2010) where they talk about the supremacy of comprehensive chromosome screening (CCS). Their published implantation rate caught my attention. They showed that when blastocyst transfer was performed they obtained an implantation rate of 70% (in 2000) in their patients and when blastocyst transfer was performed after CCS testing (in 2010) (that is transferring only euploid embryos) they obtained an implantation rate of 68.9%. But in control group where no CCS testing was performed they got only an implantation rate of 44.8% (in 2010). This means CCRM is able to get the same high implantation rate using blastocyst transfer (without performing CCS on them, that is, without selecting for euploid embryos) almost 10 years ago. But in 2010 when they performed blastocyst transfer without CCS (control group) they got only an implantation rate of 44.8%! I hope people get my point!!! So I decided to compare patient selection criteria used in both the studies and found not much difference.
 

2000, CCRM,  PMID: 10856474 ( publication on blastocyst transfer)         Patient selection criteria     FSH ≤ 15 mIU/ml, age ≤ 45 years atleast  10 follicles ≥ 12 mm on the day of HCG administration   Mean age     34 years   Age range     25-43   Mean number of blastocysts on day 5     8.6   Implantation Rate     70%   No of blastocysts transferred     2

2010, CCRM,  PMID: 19939370 ( publication on CCS)
Patient selection criteria			FSH  7.3-7.6 mIU/ml , patients with  AMA, RPL and RIA
Mean age			37.7 years
Age range			30-43
Mean number of blastocysts on day 5 (CCS group)			6.3
Implantation Rate (control group) Implantation Rate (CCS group)			44.8% 68.9%
No of blastocysts transferred			2 .7 (control group) 2 (CCS group)

In their 2000 publication they used blastocysts scored using morphological appearance (no selection for chromosomally normal embryos). There is not much information about the patient characteristics (like whether there are patients who underwent recurrent pregnancy loss (RPL) and implantation failure). But definitely there are patients with Advanced Maternal Age (AMA) as evidenced by the age range of patients given in the publication. But nowhere had they mentioned that the above said patients are first time IVFers! So naturally there would have been patients with previous IVF failures. 68 patients underwent 2 blastocyst transfers (top scoring blastocyst).

In 2010 publication where they applied CCS using aCGH to screen embryos, they say they have included patients with AMA, patients who underwent RPL and patients with recurrent IVF failure (RIF) (more than 2 failed IVF cycles!). They had 48 patients in CCS group and their control group consisted of 113 patients undergoing blastocyst transfer in the same center. They say that the patients were matched for age, day 3 FSH, previous unsuccessful attempt etc. But there is no mention whether there are patients with RPL in control group! It must be noted that the day 3 FSH in two groups is very less when compared to day 3 FSH of patients from 2000 paper. They said the selection criteria for including patients for blastocyst transfer (2000 publication) is day 3 FSH ≤ 15 mIU/ml. It does imply that they used patients who had FSH upto 15 mIU/ml.

If this is the case how come they got an implantation rate (with fetal heart tone) of 70% in 2000 (the same group and the same author too!) with the transfer of 2 good quality blastocyst and when they performed 3 blastocyst transfer (2.7 mean) in control group in 2010 they are able to achieve only an implantation rate (with fetal heart tone) of only 44.8%. In the CCS group they got an implantation rate of 68.9%. 

Even if they argue that they have included only the difficult patients (as per AMA, RPL and RIF) – the FSH level in patients and the blastocyst formation rate do not show much difference between the patients selected in 2000 and in 2010. Actually in 2010 paper the day 3 FSH level of patients seems to be lower than in 2000! 

The only question in my mind after comparing both their publications is - ARE THEY BIASED?