does injuring the endometrium ( with D&C or endometrial biopsy) improve ivf rates?

this is a topic that has been hotly debated over the years. The rationale behind performing a biopsy or a quick scraping of the uterus prior to IVF is that the healing that follows the scraping improves the immune profile.
2 aprroaches hve been takent to achieve this : the first is to do an endometrial biopsy on day 21 the cycle preceding the  IVF cycle , the second approach is to do a biopsy  on the day of egg retrieval. A total of 5 well designed studies was analyzed by the physicians from  Cochran database. the Cochrane Database is a non for profit. " Cochrane Reviews are unique because they are both produced by, and are relevant to, everyone interested in the effects of human health care. Based on the best available evidence.........Practitioners can find out if an intervention is effective in a specific clinical context."

The result of the review is that if the "scraping" was performed at time of retrieval , this resulted in decreased pregnancy rates . If the procedure was performed the preceding cycle resulted in  increased pregnancy and increased live birth rates.

Endometrial Injury in the luteal phase of the cycle preceding IVF  seems to improve IVF outcome , this procedure can be offered to increase chances for pregnancy when previous IVF attempts have failed.

You can locate the study here

Thin endometrial lining: how thin is too thin?

The lining  thickness is probably one of the most important parameters that predict the success of an IVF cycle

The uterine lining is the part of the uterus that sheds every months with  every menstrual cycle. It is the area where the embryo implants.

There is some debate about "how thin is too thin", as well as to "how thick is too thick". In general, 8-13 mm is good, less than 6 is potentially a problem, and greater than 15 or so might possibly reduce chances for successful pregnancy.

Additional factors can affect the lining , such as polyps, fibroids or adhesions.

Is progesterone elevation on the day of human chorionic gonadotrophin administration associated with the probability of pregnancy in in vitro fertilization?

This  is an important question. IVF cycles are  monitored with serial measurements of estrogen ,  LH ,and Progesterone. At times , towards the last day of stimulation  we observe a slight rise of progesterone. some have questioned whether this progesterone level increase ( slight increase  not majour ovulation increases of 2 or 3) reduces the chance of pregnancy.

The short answer to this question is "the best available evidence does not support an association between progesterone elevation on the day of hCG administration and the probability of clinical pregnancy in women undergoing ovarian stimulation with GnRH analogues and gonadotrophins for IVF".

This is based on a large meta analysis that you can find here

Lesley Brown, mother of first IVF baby, Louise Brown dies.

She was 64 year old. I guess we  could say this sad moment marks the change of an era.
32 years ago   scientists held their breath as they waited for news of the world's first test tube baby. When Louise Brown was born - so was IVF treatment. The doctor who gave us Louise Brown recalled looking at her in the Petri dish, and said, she was beautiful then and she’s beautiful now.”

Today, more than three million babies have been born around the world thanks to the technology which was pioneered in Britain.and Louise Brown has a baby of her own.

If you have an interest in the  history of the science of IVF i strongly recommend you watch the NPR documentary about another  famous IVF story : the story of  Doris Del-Zio , who could have  been the first woman in the world to conceive a baby through in vitro fertilization or IVF.

But things went differently.......... after the embryos were created ,  the  chairman of the Department of  OB/GYN at Columbia, Raymond Vande Wiele, went into the embryology lab at night and destroyed the embryos because he was afraid of the possible repercussions . This would have been the first IVF baby ever!

Link:  http://www.pbs.org/wgbh/americanexperience/features/transcript/babies-transcript/

Lower IVF Pregnancy Rates Widely Reported in Patients of African Origin May Be Consequence of Genetic Predisposition towards Autoimmunity

 It has long been known that ivf success rates differ amongst different races/ethnic groups. This new study suggests that predisposition to autoimmune disease may be the cause for these differences.

Despite general improvement in outcomes of fertility treatments, disparities between races/ethnicities have actually increased. Prevalence of infertility also differs in that African women experience infertility more frequently than Caucasians and Asians. Causes for these differences have remained largely unknown.
This new study, just published in the prestigious medical journal PLoS One (www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0018781), was conducted by the Center for Human Reproduction (CHR) in New York, NY, and involved 339 Caucasian, Asian and African women. As previously widely reported in the medical literature, African patients demonstrated significantly lower IVF pregnancy rates, compared to Asian and Caucasian patients, even after controlling for age and BMI. African patients also demonstrated the highest rates of the recently described FMR1 (fragile X mental retardation) gene sub-genotype het-norm/low, which the same group of researchers previously reported to be statistically highly associated with autoimmunity. Asian women, with lowest prevalence of het-norm/low experienced the highest pregnancy rates after IVF.

 

Wht is the best protocol for poor responders (diminished ovarian reserve)? A comparison of different protocols for poor responders in IVF: study.


"Poor responders" are women who have a sub optimal response to fertility drugs: they make less eggs than expected after taking fertility medication. This may be due to actual age or to premature ovarian aging.
What is the optimal stimulation protocol for poor responders? For many years people have tried different protocols such as estrogen priing , microdose Lupron , micro hcg , high fgonadotropin , low gonadotropin, clomid plus gonadotropin etc.

A doctor may try to tell you that one protocol is superior to the other but , in fact they are all very similar in outcome.

This recent study on fertility and sterility compares microdose lupron protocol to luteal phase ganarelix(Antagon or Cetrotide). the outcome of the study is no surprise: no difference between the two protocols.

abstract below.

We performed a randomized trial to compare IVF outcomes in 54 poor responder patients undergoing a microdose leuprolide acetate (LA) protocol or a GnRH antagonist protocol incorporating a luteal phase E₂ patch and GnRH antagonist in the preceding menstrual cycle. Cancellation rates, number of oocytes retrieved, clinical pregnancy rates (PR), and ongoing PRs were similar between the two groups.

source : fertility and sterility

IVF officially a sin according to Catholic Church

One of the things that puzzles me the most about the Catholic church is it's insistence on using all sort of technology at the end of life (see it's insistence of keeping people on ventilators forever when they are brain dead) and at the same time be against all form of technology to help life at it's inception.
The article is in Italian from the Italian newspaper "La Stampa". In a nutshell, the Vatican experts on sin are currently meeting to analyze new "modern" forms of sin and undergoing IVF will probably be listed as one of them.

Link:  http://www3.lastampa.it/cronache/sezioni/articolo/lstp/394249/

 

IVF not a universal solution to infertility

This is an interesting new article about the realities of infertility treatments. Although modern fertility technology is able to help most couples. For many the road to success is paved with many hurdles and pains: physical , psychological and financial.

 quoting from the article

Though outcomes differ, the constant is that the couple is unable to conceive a child through intercourse, causing feelings of shame, embarrassment and isolation. Couples often are peppered with well-meaning advice and nosy questions from friends and family.
They begin a race against a clicking biological clock.
Some couples actually get divorced after successfully achieving a pregnancy, because they have ignored their relationship for so long.
Some have drained their savings, scraping together from $20,000 to $30,000 to travel to Washington or Colorado to fulfill a dream of giving birth. If they want to try again after a failed treatment, or want more than one child, they must pay again.

link: http://billingsgazette.com/news/local/article_ccd6b4a9-a925-5ae2-8000-3103313536a9.html

Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome.

It is stll not clear not clear whether addition of metformin to stimulation protocols is beneficial. This very good review from the Cochane Database . the conclusion odf the review was that no evidence exists that metformin treatment before or during ART cycles improves live birth or pregnancy rates.

Gynecology, Federal University of São Paulo (UNIFESP), Av. Dr. Altino Arantes, 865 - ap. 124, São Paulo, Vila Clementino, Brazil, 04042-034. leotso@uol.com.br

BACKGROUND: The use of insulin-sensitising agents, such as metformin, in women with polycystic ovary syndrome (PCOS) who are undergoing ovulation induction or in vitro fertilisation (IVF) cycles has been widely studied. Suppression of insulin levels with metformin might reduce the hyperinsulinaemia and hyperandrogenism suppression of the ovarian response. As a consequence, metformin could improve both pregnancy and live birth rates. OBJECTIVES: To determine the effectiveness of metformin as a co-treatment during IVF or intra-cytoplasmic sperm injection (ICSI) in achieving pregnancy or live birth in women with PCOS. SEARCH STRATEGY: The Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, LILACS, the meta Register of Controlled Trials, and reference lists of articles were searched (to week 4, September 2008). SELECTION CRITERIA: Types of studies: randomised controlled trials (RCTs) comparing metformin treatment with placebo or no treatment in women with PCOS who underwent IVF or ICSI treatment.Types of participants: women of reproductive age with anovulation due to PCOS with or without co-existing infertility factors.Types of interventions: metformin administered before and during IVF or ICSI treatment.Types of outcome measures: live birth rate, clinical pregnancy rate, miscarriage rate, incidence of ovarian hyperstimulation syndrome (OHSS), incidence of patient-reported side effects, serum estradiol level on the day of trigger, serum androgen level, and fasting insulin and glucose levels. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data according to the protocol. The methods of randomisation and allocation concealment, and characteristics of the studied groups were evaluated. MAIN RESULTS: This review found no evidence that metformin treatment before or during assisted reproductive technique (ART) cycles improved live birth or clinical pregnancy rates. The pooled odds ratio (OR) for live birth rate (3 RCTs) was 0.77 ( 95% CI 0.27 to 2.18) and for clinical pregnancy rate (5 RCTS) was 0.71 (95% CI 0.39 to 1.28). The risk of OHSS in women with PCOS and undergoing IVF or ICSI cycles was reduced with metformin (pooled OR 0.27, 95% CI 0.16 to 0.47). AUTHORS' CONCLUSIONS: This review found no evidence that metformin treatment before or during ART cycles improves live birth or pregnancy rates. The risk of OHSS in women with PCOS and undergoing IVF or ICSI cycles was reduced with metformin. Further large RCTs are necessary to definitively answer if the use of metformin in PCOS women undergoing ART improves live birth and pregnancy rates.

source Cochrane Database Syst Rev. 2009 Apr 15;(2):CD006105.

Embryo cryopreservation (a primer)

The first pregnancy derived from a frozen human embryo was reported by Alan Trounson & Linda Mohr in 1983 (although the fetus aborted spontaneously at about 20 weeks of gestation); the first term pregnancies derived from frozen human embryos were reported by Zeilmaker et al. and the first human baby hatched via a rate frozen freezing process was born in 1984. Since then and up to 2008 it is estimated that between 350,000 and half a million IVF babies have been born from embryos controlled rate frozen and then stored in liquid nitrogen; additionally a few hundred births have been born from vitrified oocytes but firm figures are hard to come by.

On the safety of embryo cryopreservation, a 2008 study reported at the ESRE discovered that children born from frozen embryos did “better and had a higher birth weight” than children born from a fresh transfer. The study was conducted out of Copenhagen and evaluated babies born during the years 1995–2006. 1267 children born after Frozen Embryo Transfer (FET), via controlled-rate freezers and storage in liquid nitrogen, were studied and categorised into three groups. 878 of them were born using frozen embryos that were created using standard in vitro fertilisation in which the sperm were placed into a dish close to the egg but had to penetrate the egg on their own. 310 children were born with frozen embryos created using ICSI in which a single sperm was injected into a single egg, and 79 were born where the method of creation of the embryos was not known.

17,857 babies born after a normal IVF/ICSI with fresh embryos were also studied and used as a control group or reference group. Data on all of the children’s outcomes were taken regarding birth defects, birth weights, and length of pregnancy. The results of the study showed that the children who came from frozen embryos had higher birth weights, gave longer pregnancies and produced fewer “pre-term” births. There was no difference in the rate of birth defects whether the children came from frozen embryos or fresh embryos. In the FER group, the birth defect rate was 7.7% compared to the fresh transfer group which was slightly higher at 8.8%. The scientists also found that the risk for multiple pregnancies was increased in the fresh embryo transfers.

Around 11.7% of the ICSI and 14.2% of the IVF frozen cases were multiple pregnancies. In the case of fresh embryos, 24.8% of the ICSI and 27.3% of the IVF were multiple pregnancies. It should also be noted that maternal age was significantly higher in the FER group. This is significant since based on age one would have expected a higher rate of problems and birth defects. The study adds to the body of knowledge suggesting that traditional embryo freezing is a safe procedure. It was unclear however why the frozen embryo children did better than their fresh embryo counterparts

If multiple embryos are generated, patients may choose to freeze embryos that are not transferred. Those embryos are slow frozen and then placed in liquid nitrogen and can be preserved for a long time. There are currently 500,000 frozen embryos in the United States.

The advantage is that patients who fail to conceive may become pregnant using such embryos without having to go through a full IVF cycle. Or, if pregnancy occurred, they could return later for another pregnancy. Spare embryos resulting from fertility treatments may be donated to another woman or couple, and embryos may be created, frozen and stored specifically for transfer and donation by using donor eggs and sperm.

source Wikipedia

Video of Embryo Transfer

this is a video that describes pretty well the process of embryo transfer. As you will be able to see the embryo (or embryos) are gently placed with a catheter approximately 2 centimeters from the top (fundus) of the uterus. They are pretty much planted in a gelatinous substance and therefore do not fall out.

Video explanation of ivf

This one is from youtube. Video created by a doctor in india. Pretty good job

On Acupuncture and Infertility (an in depth analysis)

Below you will find an in depth analysis of the available science on acupuncture and IVF. As you probably know i am a fertility specialist with a decade of experience. I use acupuncture daily as part of my practice and my professional experience with it has been very positive . Nevertheless since i have done some reading to see what info was available online on this topic most of what i found was complete junk, advertising ,false promises and unscientific information. This makes me sad because very valuable alternative treatment options often end up on websites like quackwatch because of the misinformation that is spread around online.
Consequently I attemped to fix this problem by reading all the literature currently available on the topic and summarize it in a scientific way, as if i was presenting it to some of my colleagues. So i am sorry if the content at times appears heavy.

What is Acupuncture?

The term "acupuncture" describes a family of procedures involving the stimulation of anatomical points on the body using a variety of techniques. The acupuncture technique that has been most often studied scientifically involves penetrating the skin with thin, solid, metallic needles that are manipulated by the hands or by electrical stimulation.

Practiced in China and other Asian countries for thousands of years, acupuncture is one of the key components of traditional Chinese medicine. In TCM, the body is seen as a delicate balance of two opposing and inseparable forces: yin and yang. The concept of two opposing yet complementary forces described in traditional Chinese medicine. Yin represents cold, slow, or passive aspects of the person, while yang represents hot, excited, or active aspects. A major theory is that health is achieved through balancing yin and yang and disease is caused by an imbalance leading to a blockage in the flow of qi. Yin represents the cold, slow, or passive principle, while yang represents the hot, excited, or active principle. According to TCM, health is achieved by maintaining the body in a "balanced state"; disease is due to an internal imbalance of yin and yang. This imbalance leads to blockage in the flow of qi. In traditional Chinese medicine, the vital energy or life force proposed to regulate a person's spiritual, emotional, mental, and physical health and to be influenced by the opposing forces of yin and yang(vital energy) along pathways known as meridians. Qi can be unblocked, according to TCM, by using acupuncture at certain points on the body that connect with these meridians. Sources vary on the number of meridians, with numbers ranging from 14 to 20. One commonly cited source describes meridians as 14 main channels "connecting the body in a weblike interconnecting matrix" of at least 2,000 acupuncture points.

Source : NIH

Do I Believe In Acupuncture ?

I get asked frequently by patients if I believe in Acupuncture or other alternative treatments. My standard answer to the question is that as a scientist i have no beliefs, i just look at the evidence. Of course as a very open minded person i understand there are different levels of evidence. I also understand that absence of evidence of any treatment's efficacy is not the same thing as proven evidence that it is not efficacious. Therefore i do not discard a treatment option a priori just because there are no randomized double blind prospective studies on the topic published in the New England Journal of Medicine.

So far there have been 6 Prospective Randomized Studies on the role of acupuncture in infertility

These studies do not focus on acupuncture and fertility in general since this kind of study would be very difficult if not impossible to do. Most of the studies have focus a simple question: does acupuncture performed during IVF (In Vitro Fertilization) treatments around the time of embryo transfer (usually one session thirty minutes before and after embryo transfer) increase the chance of pregnancy?

1) The Original Study ("Paulus Study")

This research originated from an original study performed by a German group (Paulus et al.) which is cited pretty much in every website that advertises acupuncture services. In the study (the first randomized, controlled, prospective trial of acupuncture with IVF patients), published in 2002, 165 women undergoing embryo transfer were randomized to receive either 25 minutes of acupuncture or were assigned to a control group, that consisted of resting quietly for the same amount of time both before and after embryo transfer. In this study a significant increase was observed in the clinical pregnancy rate for the acupuncture arm when compared with the control arm (42.5% vs. 26.3%).

As exciting as the study was, there was an important source of criticism in it: the control group was no treatment (rest) rather than placebo (sham acupuncture). Now I do not want to spend much time here explaining what a placebo is but in a nutshell a placebo is a "sham" treatment that has no known effect on a disease, but the receiver of the treatment believes that the placebo is efficacious and thanks to the power of suggestion a treatment effect is observed.

2) The follow up study of the Paulus Group ("Second Paulus study")

Interestingly enough the same group was aware of the fact that a no treatment control group might have constituted a problem and one year later carried out a follow up study with with the placebo control. The study was presented at the annual meeting of the European Society for Human Reproduction and Embryology (ESHRE). In the follow up study 200 patients were randomized to receive either real or sham acupuncture for 25 minutes before and after the IVF Embryo Transfer. The study concluded that there was no statistical difference between the two groups ( 43% vs 37% , p=0.39 ). It is important to note that in this study good quality embryos were used.

It is important to note that the authors of the study hypothesized that the control group may have had higher than expected pregnancy rates due to a possible acupressure effect of the sham acupuncture. This is pure hypothesis though since there was no third group without therapy to compare the outcomes with.

The authors opted never to publish this study with negative outcome as full paper, this is a bit concerning because it may signal bias in favour of acupuncture.

3) The Dieterle Study

This is the third randomized prospective study, the lead author is Stefan Dieterle in Dortmund, Germany. The study included 225 patients.

The protocol consisted of 30 minutes of acupuncture after Embryo Transfer and 3 days later and the addition of a special Chinese medical drug (the seed of Caryophyllaceae) was placed on the patient’s ear at the same time. The control group received different acupuncture points, specifically designed not to influence fertility and making sure that equal numbers of needles were applied to the study and control groups.

The clinical pregnancy rate was 34% in the treatment group vs. 16% in the control group (P<.01). This astounding difference in pregnancy was noticed by the authors. More specifically in the paper they note that "according to the German IVF/ICSI register (2003), the average clinical pregnancy rates for this age are 24.6% for IVF and 22.6% for ICSI". I am quite surprised that the study was not controlled for embryo quality (in fact the words "embryo quality" are not ever mentioned in the paper) although all other major parameters such as age, weight, cause of infertility, type of stimulation, number of ampules etc.., were not statistically different. The authors do not highlight this fact although they mention that thanks to the German Embryo Protection Law, clinics are not allowed to perform embryo selection. Nevertheless this observation leaves the door open to the possibility that the treatment group could have just had better embryos by pure chance.

So rather than looking into the obvious, control for embryo quality, the authors look elsewhere to explain these discrepancies suggesting that the the sham acupuncture group could have had an adverse effect on the pregnancy rate.

4) The Danish Study

This is probably the largest randomized perspective study to date it was conducted by Dr. Lars Westergaard in Denmark and it was sponsored by the Danish government.

Dr. Westergaard randomized 300 IVF patients so that 100 received acupuncture on the day of Embryo Transfer according to the original Paulus protocol, 100 received acupuncture on the day of Embryo Transfer and again 2 days later, and a control group of 100 subjects received no acupuncture at all. The control subjects had 1 hour of bed rest after Embryo Transfer.

It is interesting to note that unlike the previous studies where acupuncture was administered by licensed acupuncturists (and often the same practitioner) in this study, 9 nurses were trained and administered the acupuncture.

Pregnancy rates: both acupuncture groups had statistically significant greater pregnancy rates with( 39% for the single-session acupuncture, 36% for the two-session) the control group that had a clinical pregnancy rate of 24%.

The ongoing pregnancy/delivery rate was statistically significantly higher in the one-session group than in the control group, but there were no differences between the two-acupuncture-session and control group. This observation, along with the observation that pregnancy loss rates were much greater in the 2 session group vs the 1 session group (although not statistically significant) brought up again the question on weather acupuncture days after transfer could potentially have adverse effects.

What I found to be really interesting about this study was the fact that the authors found no difference in implantation rates (gestational sacs/no. of transferred embryos) which is a bit surprising because the theory behind acupuncture is that it may increase implantation.

So again no mention about embryo quality in any of the groups.

Why do I think mentioning embryo quality is important? Because Acupuncture is administered after the embryos are created and therefore it is a key element in determining whether the groups of subjects being compared are really similar.

The Australian Study

228 women were randomized in two groups: acupuncture and sham acupuncture (that means not on acupuncture points known to affect fertility) with placebo needles, these newly developed needles are retractable, so the subjects are not aware of whether they are receiving real acupuncture treatment.

All subjects had three treatment sessions. The first took place on day 9 of stimulating injections, and the second and third were immediately before and after Embryo Transfer.

Although the pregnancy rate was 31% in the acupuncture group and 23% in the control group the difference did not reach statistical significance. The ongoing pregnancy rate at 18 weeks was higher in the treatment group (28% vs. 18%), but the difference was not statistically significant either.

This study also reported embryo quality, no difference of embryo quality being reported in the 2 groups.

This was a well designed and executed study that was designed after the original Paulus study (with some differences such as the day 7 acupuncture). The authors hypothesize that if they had done a study with more subjects and therefore a greater power t detect smalled differences acupuncture may have proven efficacious.

The Harvard Study

This very recent study was conducted by Dr. Alice Domar. Dr Domar is well known worldwide for heading the Mind Body Center for Women's Health at Harvard's affiliated Boston IVF. Dr. Domar was interested in trying to figure out a way to do a good acupuncture study that mimicked a well designed study using a pill. In order to do this blinding was essential so that it would be possible to rule out if the placebo effect was on the part of the patient, the health care team, or a combination of the two.

Dr Domar went about replicating the original Paulus study and to "assess the potential contribution of a placebo effect on the part of the patient, but to control for the placebo effect on the part of the health care team." For this reason all members of the health care team, not only the doctor the doctor performing the transfer(as in prior studies), were blinded to the treatment.

As per Dr. Domar's paper :

In both the Paulus and Dieterle studies the physician performing the embryo transfer was blind but the remainder of the health care team was apparently not. There was no information on staff blinding in the Smith study and in the Westergaard study , blinding could not have taken place as the actual acupuncture sessions were conducted by the clinic nurses themselves. Thus it is possible that there could have been a placebo effect on the part of members of the health care team. This is somewhat doubtful, as one would think that the member of the team who has the greatest potential impact on the results of the embryo transfer would be the physician and this was controlled for in at least two of the studies.

There were no significant differences between the two groups in terms of clinical pregnancy rates with 30.8% ultrasound-confirmed clinical pregnancy for the acupuncture compared to a 33.8% rate in the controls (P=.69).

No difference in early miscarriage rates was noted as well.

On the topic of embryo quality: "Because the Paulus study used only subjects with good quality embryos, a separate analysis was performed on subjects who had at least one good quality embryo transferred. The acupuncture patients in this subgroup had a 42% clinical PR and the control subjects had a 47% rate (P=not significant [NS])".

I was very impressed by Dr. Domar's study, mostly because she is not a member of the alternative medicine denier's gang like the people on Quackwatch. On the contrary she is the kind of person who carries out studies with titles like "Impact of group psychological interventions on pregnancy rates in infertile women", in which she proved that 10 months of psychological intervention increased pregnancy rates in infertile patients. She is the kind of researcher that you would imagine being biased towards an alternative regimen rather than against; however, she is also a good scientist who has written about the need of sticking to good science.



Final Considerations

I think that the existing evidence is suggestive that an acupuncture session at the time of embryo transfer may increase pregnancy rates in IVF. Given the quality of the studies and the fact that they appear to have some methodological limitations, such as selection bias which may have influenced the study findings, it can be argued that the existing evidence is inconclusive.

What is the mechanism of action of acupuncture in IVF?

Based on the existing science we do not really know. Various possibilities have been hypothesized: increased blood flow to the uterus, uterine relaxation (although a large ultrasound study of 163 subjects by the Paulus group confirmed acupuncture treatment does not inhibit uterine motility, interestingly this negative study was also not published and left languishing as an oral presentation at ASRM) or increased release of endorphins, and finally placebo effect.

Lets say that the effect of acupuncture on IVF is due to placebo, if i am a patient should I care?

I say that if it works for you .....you shouldn't care why it works! In fact the more you question the less it is likely to work.

I think that the issue is more relevant for practitioners and it deals more with the ethics of medicine and the philosophy of science.

My good friend Dr. Pati suggested a way to approach this: even if it is placebo effect-if it
works-use it -the power of the mind is limited only by our preconceptions-

Is there any good scientific evidence that Acupuncture may help me even if i am not doing IVF?

All of the evidence currently available at this time is anecdotal, which means that all of the claims that you read on all promotional websites are pretty much unverified claims. As I stated at the beginning of this article, this does not exclude that an effect may be present: it's just not been proven by rigorous scientific methodology (the kind of methodology and rigorous work that you expect and demand your infertility specialists to go by).

What About the Study on the British Medical Journal?

In February 2008 an Article from British Medical Journal presented a meta analysis of the existing studies (excluding the domar study) and concluded that " current estimates of the effects of adjuvant acupuncture on in vitro fertilisation are significant and clinically relevant" .

Since this article is nothing but a cumulative analysis of the above trials and overall does not contradict their outcomes i would argue that id does not add much to the discourse: ultimately if there are methodological flows in the original study a meta-analisys is not going to correct any errors.

Why has Acupuncture become so popular?

Because of the evolving nature of medicine from humanistic to science we have witnessed major change in the role of doctors. Doctors are not healers anymore, they operate according to algorithms. Because of this they are viewed as detached and not caring. So there is an enormous interest in ancient healing practices whose practitioners actually seem to "care" and "listen".

One of the major arguments in favour of acupuncture is that it has been around for thousands of years.

Most alternative treatments and especially the ones which are ancient and have survived to our times have almost no side or adverse effects: this makes a lot of sense if you think about it. Throughout the centuries many other medical treatments in use (application of leeches for example) had major side effects ,and some actually killed people. Therefore any treatments that may have had no effect or minimal effect on whichever ailment ended up appearing much more efficacious just by virtue of contrast.

References

Paulus WE, Zhang M, Strehler E, El-Danasouri I, Sterzik K. Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproduction therapy. Fertil Steril.

Paulus WE, Zhang M, Strehler E, Seybold B, Sterzik K. Placebo-controlled trial of acupuncture effects in assisted reproduction therapy. 2003: Oral presentation, ESHRE, Madrid, Spain, June 2003;18(Suppl1): xviii18.

Dieterle S, Ying G, Hatzmann W, Neuer A. Effect of acupuncture on the outcome of in vitro fertilization and intracytoplasmic sperm injection: a randomized, prospective, controlled study. Fertil Steril. 2006;85:1347–1351.

Smith C, Coyle M, Norman RJ. Influence of acupuncture stimulation on pregnancy rates for women undergoing embryo transfer. Fertil Steril. 2006;85:1352–1358.

Westergaard LG, Mao Q, Krogslund M, Sandrini S, Lenz S, Grinsted J. Acupuncture on the day of embryo transfer significantly improves the reproductive outcome in infertile women: a prospective randomized trial. Fertil Steril. 2006;85:1341–1346.

Domar a., Meshay I, Kelliher J, Alper M, Powers D. The impact of acupuncture on in vitro fertilization outcome. Fertil Steril. 2008; march

Gleicher n. , et al. Background pregnancy rates in an infertile population. Hum Reprod. 1996 May;11(5):1011-2.

Copyright © 2008 Andrea Vidali  All rights reserved.

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.