Cleavage stage ("day 3") versus blastocyst stage ("Day 5") embryo transfer in assisted conception.

A recent cochrane database review tackled this topic here is a summary of the findings below:

Abstract

Background

Recent advances in cell culture media have led to a shift in IVF practice from early cleavage embryo transfer to blastocyst stage transfer. The rationale for blastocyst culture is to improve both uterine and embryonic synchronicity and self selection of viable embryos thus resulting in higher implantation rates.

Objectives

To determine if blastocyst stage embryo transfers (ETs) affect live birth rate and associated outcomes compared with cleavage stage ETs and to investigate what factors may influence this.

Search strategy

Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, Cochrane Controlled Trials Register (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and Bio extracts. The last search date was January 2007.

Selection criteria

Trials were included if they were randomised and compared the effectiveness of early cleavage versus blastocyst stage transfers.

Data collection and analysis

Of the 50 trials that were identified, 18 randomised controlled trials (RCTs) met the inclusion criteria and were reviewed. The primary outcome was rate of live birth. Secondary outcomes were rates per couple of clinical pregnancy, multiple pregnancy, high order pregnancy, miscarriage, failure to transfer embryos and cryopreservation. Quality assessment, data extraction and meta-analysis were performed following Cochrane guidelines.

Main results

Evidence of a significant difference in live-birth rate per couple between the two treatment groups was detected in favour of blastocyst culture (9 RCTs; OR 1.35, 95% CI 1.05 to 1.74 (Day 2/3: 29.4% versus Day 5/6: 36.0%)). This was particularly for trials with good prognosis patients, equal number of embryos transferred (including single embryo transfer) and those in which the randomisation took place on Day 3. Rates of embryo freezing per couple was significantly higher in Day 2 to 3 transfers (9 RCTs; OR 0.45, 95% CI 0.36 to 0.56). Failure to transfer any embryos per couple was significantly higher in the Day 5 to 6 group (16 RCTs; OR 2.85, 95% CI 1.97 to 4.11 (Day 2/3: 2.8% versus Day 5/6: 8.9%)) but was not significantly different for good prognosis patients (9 RCTs; OR 1.50, 95% CI 0.79 to 2.84).

Authors' conclusions

This review provides evidence that there is a significant difference in pregnancy and live birth rates in favour of blastocyst transfer with good prognosis patients with high numbers of eight-cell embryos on Day three being the most favoured in subgroup for whom there is no difference in cycle cancellation. There is emerging evidence to suggest that in selected patients, blastocyst culture maybe applicable for single embryo transfer.

My Comments

I think the key words on the author conclusion are "good prognosis patient". that means somebody who had many eggs and many embryos were created. This allows the option of selecting the very best embryos to transfer and obviously increase the chance of a pregnancy for that cycle (possibly foregoing the chance of subsequent frozen cycles). But in the scenario of somebody with 4 average to poor quality embryos on day 3 , attempting to grow them to blastocyst stage is probably not going to change the overall prognosis. What might happen instead it that the embryos may not grow to the fifth day and the patient may not have a transfer: as frustrating as this experience is this may possibly be a better outcome than having a day 3 transfer and going to the whole 14 days of progesterone injections and get a negative beta.

Caffeine and Miscarriages

Today the International Herald Tribune had an article on caffeine and miscarriages. Parts of the article are below.

Too much caffeine during pregnancy may increase the risk of miscarriage, a new study says, and it suggests that pregnant women may want to reduce their intake or cut it out entirely.

Many obstetricians already advise women to limit caffeine, though the subject has long been contentious, with conflicting studies, fuzzy data and various recommendations given over the years.

The new study, being published Monday in the Journal of Obstetrics and Gynecology, finds that pregnant women who consume 200 milligrams or more of caffeine a day - the amount in 10 ounces of coffee or 25 ounces of tea - may double their risk of miscarriage. Ten ounces is equivalent to about 300 milliliters.

Professional groups like the American College of Obstetricians and Gynecologists and the American Society for Reproductive Medicine have not taken official positions on caffeine, representatives said.

On Friday, the March of Dimes Web site said most experts agreed that the amount of caffeine found in 8 to 16 ounces of coffee a day was safe. It noted that some studies had linked higher amounts to miscarriage and low birth weight, but stated: "However, there is no solid proof that caffeine causes these problems. Until more is known, women should limit their caffeine intake during pregnancy."

Now, having reviewed the new study, the March of Dimes plans to change its message, to advise women who are pregnant or trying to conceive to limit their daily caffeine intake to 200 milligrams or less, said Janis Biermann, its senior vice president of education and health promotion.

Li's study included 1,063 pregnant women who were interviewed once about their caffeine intake. At the time of the interview, their median length of pregnancy was 71 days. But 102 had already miscarried - not surprising, because most miscarriages occur very early in pregnancy. Later, 70 more women miscarried, for an overall miscarriage rate of 16 percent for the group, a typical rate.

Of 264 women who said they used no caffeine, 12.5 percent had miscarriages. But the miscarriage rate was 24.5 percent in the 164 women who consumed 200 milligrams or more per day. The increased risk was associated with caffeine itself and not with other known risk factors like the mother's age or smoking habits, the researchers said.

Li said the study had answered an important question that previous research had left unresolved. Women who have morning sickness are less likely to miscarry than those who do not, possibly because the same hormonal changes that cause nausea and vomiting contribute to a healthy pregnancy. But some researchers said morning sickness could lead to misleading results in caffeine studies.

These researchers argued that because they feel ill, some women may consume less caffeine. That tendency may make it appear that they are less likely to miscarry because they avoid caffeine, when the real reason is actually that they started out with healthier pregnancies.

Li said he and his colleagues had carefully analyzed the data and determined that the risk from caffeine was real and could not be explained away by different rates of morning sickness.

Dr. Carolyn Westhoff, a professor of obstetrics and gynecology, and epidemiology, at Columbia University Medical Center in New York, had reservations about the study, noting that miscarriage is difficult to study or explain.

She said most miscarriages resulted from chromosomal abnormalities, and there was no evidence that caffeine could cause those problems.

Of course Dr. Westhhoff is dead on with her comments. The study is at best mildly indicative of an effect . The main reason is that it is a retrospective study . To believe that cutting caffeine would reduce miscarriages by 50% is simply ludicrous.
Nevertheless i would say that it is prudent to reduce caffeine intake to 2 cups per day of regular coffee. That's 1 espresso or 1 "tall latte" for the starbucks drinkers.

Young cancer victims are being denied access to NHS fertility treatment, according to a report by leading doctors in the UK

http://uk.news.yahoo.com/skynews/20080115/tuk-nhs-cancer-treatment-fails-young-vic-45dbed5.html