Singleton – Twins – Triplets – Quadruplets – Quintuplets –Sextuplets – Septuplets –

Ken Drury, Ph.D., Editor 

Higher Order Multiples (HOM) is a term used to denote pregnancies brought about by the multiple implantation of embryos which in many cases have been conceived through the use of one type or another of Assisted Reproductive Technologies (ART). These pregnancies, more often than not, lead to premature births resulting in morbid and/or deadly outcomes. A working definition of HOM is generally accepted as an ongoing gestation comprised of three or more fetuses, whether or not all are viable and able to survive to term.The public has been awed in the past by sensational reports of HOM births stemming from either natural means (Dionne quintuplets born May 28, 1934 – the first quintuplets known to survive infancy and the only all female identical set of five ever) or more recently through fertility drug treatment (sextuplet babies born to the Hayes family in 2004; as well as, the McCaughey septu plets – born November 19, 1997) These reported events brought generally sympathetic, if not congratulatory responses, from the public at large.

Unfortunately, in the case of the Dionne Quints, these children wound up as wards of the State and later as a circus “side-show”. So, what are we to make of the latest media-storm over the birth of Octuplets in California? Is there any current accurate information available to help us assess this phenomenal event?

The only thing certain at the present time is that there are eight premature sibling infants residing in a California NICU unit with a mix of six brothers and sisters awaiting them in a mortgage threatened house surrounded by a firestorm of media attention. (Four of the eight infants were released from hospital at time of press. -Ed.)

Of course, we as reproductive specialists are stunned by this shocking news and need to understand in more detail (as soon as possible) what the actual facts surrounding the use of ART treatment were in this particular case. We must also begin to assess the impact of this event on our own infertility practices and what it may bring to our profession.

In particular, how should laboratory personnel (from directors, supervisors, technologists and technicians) respond to the news that six embryos (Frozen or Fresh?) were loaded into a catheter and transferred to the uterus of a 34 year old women who had already demonstrated (superb) fecundity on several previous occasions? I will return to this question in just a bit. However, although this remains a valid question, we have to ask ourselves if the above event actually took place in the manner it has been reported?

The infertility clinic reported to have provided the ART expertise in this occasion was headed by a non-specialized OBGYN physician who was also grand-fathered into the position of laboratory director. The SART success rate for this program, reported for the year 2007, was the worst of any of the approximately 400 plus clinics in America (3/37 = 8% live births per cycle). It is all the more astonishing since this program’s implantation rate was an anemic 3% even when transferring on average 4 embryos per case in this patient’s age bracket (<35).

The fact that the worst cases of HOM births taking place within the last two decades did not originate from IVF or the transfer of embryos, and that it has not been confirmed that there are actually identical twins involved in the birth of these (Octuplet) infants, raises the question of how exactly were these babies conceived.

It has been suggested in the blog section of the Los Angeles Times,  http://latimesblogs.latimes.com/lanow/2009/02/the-american-so.html”>http://latimesblogs.latimes.com/lanow/2009/02/the-american-so.html, (Medical group examining Beverly Hills fertility doctor in octuplets case by Shelby Grad 3:52 PM | February 10, 2009 http://latimesblogs.latimes.com/lanow/2009/02/the-american-so.html ) that this physician, while trying to raise his overall ART success rates, simply used artificial insemination to produce this Octuplet pregnancy. Is it unreasonable to think that Ms. Seulman would not understand the difference between hormonally stimulated intrauterine insemination (IUI) and IVF, especially if she were told it was IVF. Below is a more cynical perspective offered by one of the article’s blog responders:

“Let’s get real. Octomom has not shown herself to be honest or trustworthy. False and misleading statements,hiding information, excess cash for spending on luxury items (plastic surgery, fake nails, hotel room). Multiple aliases and heavy use of welfare and disability for herself (disability from a government hospital job) and for kids (for ADHD?) She is clearly not one to shy from any scam. This guy, the doctor, probably did not implant a single embryo into Suleman. The eight kids are most likely the result of using too much fertility drugs on a ‘patient’ who is relatively young and fertile. Most likely he paid her to be an advertisement for his otherwise very unsuccessful fertility clinic. And got on television in 2006 doing just that. Come on, you guys are reporters, not transcribers. The real question is who is the father. Dr. Kamrava? Grandfather Ed (Adnan?) Daoud (David?) Suleman (Soloman?)(yuck) Or someone else? The taxpayer needs to know so he can contribute to the cost of these kids.” Posted by: CalvinB | February 13, 2009 at 11:40 AM .

All this aside, it is certainly “conceivable” that this Octuplet incident did take place in the manner described by most news broadcasts; that is, by using IVF and the transfer of “extreme” numbers of embryos. If this is the case, what responsibilities do IVF laboratory personnel share with any infertility physician performing embryo transfers?

Within our professional societies, there are published guidelines issued (American Society of Reproductive Medicine (ASRM); Society of Assisted Reproductive Technology (SART)) which present reasonably clear scenarios and suggestions pertaining to the transfer of embryos (Fertil Steril 90:S163–164 2008). Other important reports on this subject have come from the respected national organization Resolve (also see: Blastocyst culture and transfer in clinical-assisted reproduction-infertility treatment and multiplegestation pregnancy, A Publication of RESOLVE:The National Infertility Association http://www.resolve.org/site/Doc-Server/Multiple-Gestation-Pregnancy.pdf?docID=621).

At the same time, individual IVF-ET programs should evaluate their own data to identify patient-specific, embryo-specific, and cycle-specific determinants that may influence the likelihood of implantation and live birth during a particular treatment case. This is important in order to develop embryo transfer policies that minimize the occurrence of HOM gestations.

Resolve’s Practice Committee Opinion also reviews the published literature relating to the potential benefits, pitfalls, and risks of blastocyst culture. These are not laws, but they do make a strong case for the curtailment of HOM pregnancies, especially when the question addresses how many embryos should be considered for transfer.

Laboratory personnel need to be well informed about the contents and rational contained in these particular guidelines and be able and willing to share them with the transferring physician if the need arises. Knowledge of current pertinent literature can also have important benefits as illustrated in a study presented in Human Reproduction by Roberto Matorras et al. (2005, 20#10:29232931) entitled:

The implantation of every embryo facilitates the chances of the remaining embryos to implant in an IVF programme: a mathematical model to predict pregnancy and multiple pregnancy rates. Within this article, the authors state “We recommend using the aforementioned formula to quantify the pregnancy rate and the risk of multiple pregnancy in the counseling of the infertile couple at embryo transfer. Such a formula is freely avail able at www.ifca.unican.es/matorras/mathpreg/ “.

Individual infertility programs likewise should discuss situations or conditions which may arise that could influence or alter the implementation of these guidelines. In general, consideration should be given to the transfer of fewer blastocyst stage embryos than cleavage stage embryos, particularly in women with excellent prognoses and high-quality blastocysts (Guidelines for the number of embryos to transfer following in vitro fertilization No. 182, September 2006 in Int J Gynaecol Obstet. 2008 Aug;102(2):203-16).

Why is it important for laboratory personnel to be up to date and knowledgeable about not only the technical aspects of gamete preparation, embryo culture, and proper transfer techniques but also the medical and ethical implications of infertility treatment? It is because every member of the laboratory (Director, Supervisor, Technologist, Technician and Trainee) is a key individual of the overall patient treatment team. Each provides expertise in critical areas of laboratory function responsible for the production of viable embryos, as well as, important information concerning specific characteristics of embryo development taking place during a particular procedure.

To put this in perspective, here is a statement taken from a website instructing infertility patients about issues surrounding the embryo transfer procedure:

“Transferring Embryos to the Uterus – Embryos are transferred on either day three or day five of development. The embryologists at GRS are highly-skilled in identifying “healthy” embryos and in some cases will recommend that a patient extend embryo development to day five, known as the blastocyst stage. Blastocyst transfer has become quite common in IVF cycles as it can increase chances for success while decreasing the likelihood of multiples. Your physician will work closely with the embryologists to determine if a day three or day five transfer would be ideal for your cycle. The transfer of several embryos increases the probability of success. A multiple embryo transfer also increases the risk of a multiple pregnancy. Any multiple pregnancy carries an increased risk of miscarriage(s), premature labor and premature birth as well as an increased financial and emotional cost. Pregnancy-induced high blood pressure and diabetes are more common in women pregnant with more than one fetus. Prolonged hospitalization may be necessary for these pregnant women and for the mother and babies after delivery.

Tubal (ectopic) pregnancy is also possible, and a combination of normal pregnancy and ectopic pregnancy may occur. A tubal pregnancy is a condition that may require laparoscopy or major surgery for treatment.” (Georgia Reproductive Specialists – http://www.ivf.com/overview.html ).

This is heavy responsibility indeed, and the lives of patients and resulting offspring can, in many cases, be directly connected to the IVF Laboratory. Let there be a prominent notice placed in your laboratory that reads: “Our Laboratory Embryologists work closely with your physician to bring about the best and healthiest infertility treatment outcome possible”. This means providing your physician with the laboratory skills and ethical commitment that go hand in hand with producing happy healthy families.

Remember, the time of transfer is not the ideal occasion to have patients considering for the first time how many embryos to have transferred. Patients need to be well aware of your program’s policy concerning the number of embryos generally considered for transfer and how these policies may relate to them specifically. Every program should also have an infertility psychologist available to counsel patients concerning this most important aspect of their treatment.

All of these considerations will impact the quality of your program as well as the overall field of infertility treatment.

Before leaving you, please check the “Letters to the JCE Editor” section and begin to formulate your own questions and comments to the articles you read here in JCE.

Also, I welcome a new member to our JCE Editorial Board: Dr. Alan Thornhill, Ph.D. HCLD from The London Bridge Fertility Centre in London England. Dr. Thornhill is the first board member residing outside the United States and we look forward to Alan’s contributions to our Journal. Please check out his Bio and contact information in this issue and on the JCE Website: www.embryologists.com.