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.

Are Doctors Miracle Workers?

Interesting article on the New York Times this weekend by David Rieff on the topic of patient physician relationship. Here are a couple of thoughts. More to follow.

Trust Your Doctor?
The article by David Rieff , "Miracle Workers?" , highlights the erosion of the concept of "trust" towards one's physician. Paraphrasing George Simmel, inherent to the nature of trust is an element of faith. This faith is ‘conditional’, in the sense that it rests on the awareness that certain social and legal structures are in place to protect one's interests. One can trust because society is organized to prevent such trust from being abused. Nevertheless, trust entails a relationship between two parties that are on different levels of knowledge and power. When medicine was a humanistic science, doctors were regarded to be the exclusive keepers of their knowledge. This was essential to a patient’s trust.

The ‘exclusivity’ of a doctor’s knowledge no longer exists. Furthermore, modern clinical epistemology has moved the medical discourse from the realm of the "possible" (as I often say to my patients, the answer to any possibilistic question is always yes) to the realm of the “probable”, that is, the quantifiable world of statistics. This shift has been quite positive, allowing more sick people to be treated with more appropriate treatments. In this new paradigm, hope is rooted not in his faith but in knowledge that we are receiving the best treatment available against our disease.

Yet patients still have a longing for the days in which they could simply "trust" their doctor. This longing is partially fulfilled today by alternative medicine, whose language remains the language of the "possible" - the language of faith. Perhaps there is a fundamental human need involved, which the language of the probable and the ‘comfort of statistics’ can never fully assuage.

Effect of cell phone usage on semen analysis: observational study

Another report on cell phone use and male fertility. I had previously reported on this topic on this blog.
This article published on Fertility and Sterility this month (2/2008) is from a reputable institution the Cleveland Clinic and i think it's findings are quite relevant. Here is the Abstract below

Objective

To investigate the effect of cell phone use on various markers of semen quality.

Design

Observational study.

Setting

Infertility clinic.

Patient(s)

Three hundred sixty-one men undergoing infertility evaluation were divided into four groups according to their active cell phone use: group A: no use; group B: <2>4 h/day.

Intervention(s)

None.

Main Outcome Measure(s)

Sperm parameters (volume, liquefaction time, pH, viscosity, sperm count, motility, viability, and morphology).

Result(s)

The comparisons of mean sperm count, motility, viability, and normal morphology among four different cell phone user groups were statistically significant. Mean sperm motility, viability, and normal morphology were significantly different in cell phone user groups within two sperm count groups. The laboratory values of the above four sperm parameters decreased in all four cell phone user groups as the duration of daily exposure to cell phones increased.

Conclusion(s)

Use of cell phones decrease the semen quality in men by decreasing the sperm count, motility, viability, and normal morphology. The decrease in sperm parameters was dependent on the duration of daily exposure to cell phones and independent of the initial semen quality.

I do not think in modern society most people would be able to survive without cell phones. These phones operate between 400 MHz and 2000 MHz frequency bands and emit radiofrequency electromagnetic waves (EMW). Reports of potential adverse effects of radiofrequencyelectromagnetic waves have been reported for a few years now with the gretest concern for the brain.

As the article states

These phones operate at different frequencies in different countries and continents. Exposure of radiofrequency energy depends upon the frequency of the cellular phone. Analog phones operate at 450–900 MHz, digital phones (Global System for Mobile Communications [GSM]) at 850–1900 MHz, and third-generation phones at approximately 2000 MHz . For years the cell phone companies have assured people that cell phones are perfectly safe. For assessing exposure from transmitters located near the body, the most useful quantity is the specific absorption rate (SAR), the amount of radiofrequency energy absorbed from the phone into the local tissues. The SAR of cell phones varies from 0.12 to 1.6 W/kg body weight depending upon the model. In the United States, the upper limit of SAR allowed is 1.6 W/kg .

So pretty much by now we have evidence that excessive phone use may have adverse health effects. I think this study is very relevant because it is the first study that showed what we in medicine call a dose-response relationship . That is the more cell phone usage the less the sperm. For the record the highest users in the study talked on the cell for more than 4 hours per day but an effect was already seen in men who talked for less than 2 hours a day. In the control group were men who reported no cell phone use ( i wonder where they found these guys id did not think they exhisted!)
the study has some limitations: most notably cell use was self reported , and everybody had a different phone, and no account was taken for where the phone was kept when not in use. Nevertheless the message is clear : "The decrease in sperm parameters was dependent on the duration of daily exposure to cell phones and independent of the initial semen quality".

So what to do?
1) Cut down phone use to less than 2 hours/day .
We are frequently lazy. I personally reach for the cell even when i am sitting in my office
2) Do not Keep the phone in your pocket.
Those belt carriers may make you look a bit nerdy but at least you are not applying the phone directly to your testicles!
3) Get a Phone with lower emissions!
Check the information provided below to figure out which phone is best for you.

Below Is The Information that You need if you want to learn more about cell phone emissions
(source: Federal Communication Commission)

Cellular Phone Specific Absorption Rate

The SAR is a value that corresponds to the relative amount of RF energy absorbed in the head of a user of a wireless handset. The FCC limit for public exposure from cellular telephones is an SAR level of 1.6 watts per kilogram (1.6 W/kg). Specific Absorption Rate (SAR) for Wireless Phones and Devices Available at various Web sites.

The easiest way to ascertain SAR for many cellular phones is via the FCC's links to individual manufacturers' Web sites: http://www.fcc.gov/cgb/sar/. On this page you will find links to most manufacturers' Web pages that include SAR information for their phones, along with instructions on how to search each site for SAR information.

You can also obtain SAR information on many cellular phones from the FCC's database if you have the FCC ID number of the phone or device and if it was produced and marketed within the last 1-2 years.

The FCC ID number is usually shown somewhere on the case of the phone or device. In many cases, you will have to remove the battery pack to find the number. Once you have the number proceed as follows. Go to the following Web site: https://fjallfoss.fcc.gov/oetcf/eas/ . Once you are there you will see instructions for inserting the FCC ID number. Enter the FCC ID number (in two parts as indicated: "Grantee Code" is comprised of the first three characters, the "Equipment Product Code" is the remainder of the FCC ID). Then click on "Start Search." The grant of equipment authorization for this particular ID number should appear. Look through the grant for the section on SAR compliance, certification of compliance with FCC rules for RF exposure or similar language. This section should contain the value(s) for typical or maximum SAR for your phone.

For portable phones and devices authorized since June 2, 2000 , maximum SAR levels should be noted on the grant of equipment authorization. For phones and devices authorized between about mid-1998 and June 2000, detailed information on SAR levels is typically found in the "exhibits" associated with the grant of equipment authorization. Therefore, once a grant is accessed these exhibits can be viewed by clicking on the appropriate entry labeled "View Exhibit."

Electronic records for FCC equipment authorization grants were initiated in 1998. Therefore, prior to this date FCC records for grants are in the form of paper records that are not part of our electronic database. At this time, due to staff limitations, we are unable to routinely search through FCC paper records to extract SAR information for grants filed prior to mid- to late-1998.

If you want additional consumer information on safety of cell phones and other transmitting devices please consult the information available below at this Web Site. In particular, you may wish to read or download our OET Bulletin 56 (see "RF Safety Bulletins") entitled: "Questions and Answers about Biological Effects and Potential Hazards of Radiofrequency Electromagnetic Fields." If you have any problems or additional questions you may contact us at RF Safety (rfsafety@fcc.gov) . [ July 18, 2000 ]

You may also wish to consult a consumer update on mobile phone safety published by the U.S. Food and Drug Administration (FDA) that can be found at: www.fda.gov/cdrh/phones .

What are the most appropriate treatments for patients with Polycystic Ovary Syndrome (PCO) who desire fertility?

Well ASRM and ESHRE had a consensus meeting last year and here is the abstract (most important points highlighted in bold by me):

Consensus on infertility treatment related to polycystic ovary syndrome.

The treatment of infertile women with polycystic ovary syndrome (PCOS) is surrounded by many controversies. On the basis of the currently available evidence, a group of experts reached a consensus regarding the therapeutic challenges raised in these women. Before any intervention is initiated, preconceptional counseling should be provided emphasizing the importance of lifestyle, especially weight reduction and exercise in overweight women, smoking, and alcohol consumption. The recommended first-line treatment for ovulation induction remains the anti-estrogen clomiphene citrate (CC). Recommended second-line intervention, should CC fail to result in pregnancy, is either exogenous gonadotropins or laparoscopic ovarian surgery (LOS). The use of exogenous gonadotropins is associated with increased chances for multiple pregnancy, and, therefore, intense monitoring of ovarian response is required. Laparoscopic ovarian surgery alone is usually effective in less than 50% of women, and additional ovulation induction medication is required under those circumstances. Overall, ovulation induction (representing the CC-gonadotropin paradigm) is reported to be highly effective with a cumulative singleton live-birth rate of 72%. Recommended third-line treatment is in vitro fertilization (IVF). More patient-tailored approaches should be developed for ovulation induction based on initial screening characteristics of women with PCOS. Such approaches may result in deviation from the above mentioned first-line, second-line, or third-line ovulation strategies in well-defined subsets of patients. Metformin use in PCOS should be restricted to women with glucose intolerance. Based on recent data available in the literature, the routine use of this drug in ovulation induction is not recommended. Insufficient evidence is currently available to recommend the clinical use of aromatase inhibitors for routine ovulation induction. Even singleton pregnancies in PCOS are associated with increased health risk for both the mother and the fetus.

Source : Fertility And Sterility via MEDLINE

I think it is very important to note that this consensus document confirms what most reproductive endocrinologists already know and that is that Metformin (Glucophage) is a lousy fertility drug. For a while it seemed to be very promising and at some point it was being prescribed (by some) to all PCOS patients. But today it is quite clear that only a subgroup of patients will benefit from this drug. More on this in the future!

Clomiphene citrate and intrauterine insemination (IUI): how well does it work?

For those of you out there who have questions on Clomid (Clomiphene Citrate , Serophene) and it's efficacy here is an excellent piece of research out of Harvard Medical School. It is a retrospective study and therefore has limitations but i think it gives a great idea of what the chances are of concieving with clomid. Here is the abstract below (Source Fertility and Sterility via MEDLINE). As usual relevant parts are Highlighted in bold by me.

Clomiphene citrate and intrauterine insemination: analysis of more than 4100 cycles.

OBJECTIVE: To evaluate the outcomes of a large cohort of patients undergoing fertility treatment with clomiphene citrate and intrauterine insemination. DESIGN: A retrospective cohort study. SETTING: Boston IVF, a large university-affiliated reproductive medicine practice. PATIENT(S): A total of 4,199 cycles performed in 1,738 infertility patients between September 2002 and July 2007. INTERVENTION(S): All patients received oral clomiphene citrate, and patients with completed cycles had intrauterine insemination performed. MAIN OUTCOME MEASURE(S): Cumulative and per cycle pregnancy rates achieved among subsets of patients defined by age, completed cycles, and intention to treat (ITT). RESULT(S): For women under age 35 years, 2,351 cycles were initiated in 983 patients. A total of 238 pregnancies ensued, yielding a pregnancy rate (PR) per completed cycle of 11.5% and 10.1% per cycle initiated with ITT. In women aged 35-37 years, 947 cycles in 422 women lead to a PR per completed cycle and ITT of 9.2% and 8.2%, respectively. For patients aged 38-40 years, 614 cycles in 265 women lead to a PR per completed cycle and ITT of 7.3% and 6.5%, respectively. In women aged 41-42 years, 166 cycles in 81 patients lead to a PR per completed cycle and ITT of 4.3% and 3.6%, respectively. For women above age 42 years, 120 cycles in 55 patients lead to a PR per completed cycle and ITT of 1.0% and 0.8%, respectively. On a per-patient treated basis, cumulative PRs were 24.2% under age 35, 18.5% ages 35-37, and 15.1% ages 38-40, whereas only 7.4% ages 41-42 and 1.8% above 42 became pregnant (one pregnancy in 55 patients). CONCLUSION(S): As anticipated, younger patients have a higher PR per cycle than older patients. The PR per cycle for patients who initiate only one or only two treatment cycles is notably higher than the corresponding per cycle rates for cycles 3 through 9. The drop in success per patient among 41- and 42-year-olds is sharp, but the exceptionally low success rate above age 42 suggests that CC with IUI has virtually no place in their treatment.

Overall this is a very good article. I am not sure i agree 100% with all of its conclusions which are a bit drastic.
I do agree, and other data supports this, that most people who get pregnant on clomid get pregnant on the first 3 cycles.
I think that the overall pregnancy rates may vary for different populations and depending on the way physicians practice. For example in my practice were we do not immediately jump to ivf pregnancy rates for inseminations are consistently higher. Some ivf physicians divert patient who have poor prognoses to iui in order not affect their center's pregnancy rates and this lowers the iui rates.
The issue on how to approach the over 42 patients is complex and furthermore (sadly) much has to deal with insurance coverage and resources. Over 42 patients are a heterogeneous group : a minority of them have good ovarian reserve whereas the majority has poor or no reserve. Although patients are very aware of this reality they often opt to try their luck. Obviously this represents a philosophical decision: the pragmatist will opt for oocyte donation whereas the more idealistic will try with their own eggs and a few lucky ones will succeed.
For what pertains the actual benefit of utilizing ovulation induction in the patients over 44 I think the verdict is still not out.

Three-parent embryo formed in lab

BBC News reports that a Newcastle University team created embryos from 3 parents

Within hours of their creation, the nucleus, containing DNA from the mother and father, was removed from the embryo, and implanted into a donor egg whose DNA had been largely removed.

The only genetic information remaining from the donor egg was the tiny bit that controls production of mitochondria - around 16,000 of the 3billion component parts that make up the human genome.

The embryos then began to develop normally, but were destroyed within six days.

for most of us who work in the field this experiment is no news at all since this is very similar work that was carried out in 2002 called Ooplasmic Transfer also known as Cytoplasm Transfer for the purpose of egg rejuvenating. Sadly the FDA put an end to this excellent and promising work.So once again the US government hampers US research and allows the brits to take over . This is exactly what happened with the first IVF . If you have time check out this brilliant link to PBS on The First IVF and discover how we missed an opportunity.

Ultimately this is work of great interest because it represents an example of human genetic engineering that is applicable and because it is for now limited in it's scope to the treatment of "orphan" (rare) conditions such as mitochondrial diseases .

Surge in older women seeking IVF

The British Human Fertilisation and Embryology Authority reported that here has been a huge rise in demand for fertility treatment among women in their forties.

The BBC News reports that Human Fertilisation and Embryology Authority figures show last year there were 6,174 treatment cycles among women aged 40-45 using their own eggs.In 1991, the comparable figure was just 596 cycles.

check out the data below (source BBC)

1991:
Women aged 40: 210 treatment cycles
Women aged 41: 153
Women aged 42: 115
Women aged 43: 55
Women aged 44: 44
Women aged 45: 19

2006:
Women aged 40: 2,288 treatment cycles
Women aged 41: 1,605
Women aged 42: 1,070
Women aged 43: 682
Women aged 44: 358
Women aged 45: 171

All forms of fertility treatment using own fresh eggs or frozen embryos

Of course this number does not surprise us since we have been observing the same phenomenon in the US. The surge in demand for fertility treatments by older patients is to be put in relation to changing demographics as a consequence of baby boomers
getting older . By definition the last baby boomers were born in 1964 and they are now 43 year old. the next generational wave is of much smaller dimension. these numbers will not change until 20012 according to demographers.