And you were told that your embryos were “good enough to freeze”. Maybe good enough to freeze but not to thaw? What went wrong? A doctor-patient conference should be the immediate next step and the savvy patient will be able to learn enough from this meeting to help her decide how to proceed with future treatment.

Embryo cryopreservation – the basics: Once an egg has been fertilized (either by conventional insemination or via ICSI,the injection procedure) it must divide and develop for five days before it becomes a blastocyst – the stage at which it may initiate implantation. The preembryo or 2PN stage is observed on “Day 1″. Days 2 and 3 denote the cell stages. The cells continue to divide but compact into an amorphous morula on Day 4 and, by Day 5 or 6, a healthy blastocyst will demonstrate sufficient stem cells to make a human being. An embryo can be successfully frozen on any of these days but the ultimate potential of this tissue depends upon its genetic normalcy, the day upon which it was frozen, and the freezing method that was employed.

An average of 50-60% of all growing embryos normally arrests between days 3 and 4 because of genetic incompatibilities of the eggs and sperm that formed them. (This percentage increases as a woman ages.) Cryopreserving cell-stage embryos (before this selection has occurred) may therefore be creating false hope in the freezer as particular embryos frozen on day 2 or 3 may have been destined to arrest in the first place.

The day on which an embryo is frozen will also affect its ability to survive once thawed. Embryos freeze and thaw well at the 2PN and blastocyst stages with survival upwards of 90%. Cell-stage embryos, however, fare far worse as only about 25% of these survive with all their cells intact. A higher percentage of thawed cell-stage embryos may initially survive but with a loss of 50% of their cells, and a patient may be a recipient of these “technically viable” embryos which have no chance of proceeding to pregnancy.

The aforementioned percentages represent the traditional “slow-freeze” method of embryo cryopreservation. This reliable technique is being replaced in most IVF centers with the newer vitrification method. To date, thaw and pregnancy rate numbers are better with vitrification but there is not yet enough data demonstrating, definitively, its superiority over the slow-freeze method.

Armed with the above the disappointed patient should meet with her doctor to review sequential photos of her embryos and to discuss the particulars of her case. How many embryos were frozen, at what stage, and by what technique? Were these supernumary embryos a step down in quality from the ones that had been formerly transferred on a fresh cycle? Does the abysmal outcome portend similar failures in subsequent attempts?

Oftentimes patients are told that they may discuss their concerns with their doctor in 3 – 4 weeks. This lengthy wait serves only to prolong anxiety and compromise trust in the physician. If the doctor cannot meet with the patient within a day or two of the cancelled transfer a phone call or even a letter from him/her (personal, private, Fed Ex if necessary!) will suffice. It is the patient’s right to request a dialogue. Communication is key.

The Web is replete with strategies on how to navigate and survive the Infertility Inquisition: seek solace and strength from your partner or spouse and together devise a script that you can “volley back” when served the dreaded probing questions. Alternatively do not answer the questions at all. Decline social invitations. Avoid venues that are certain to attract crowds and children. You are encouraged to celebrate with a childless couple – sounds like your “giving back” contribution for the year. (Is it tax-deductable?) Above all – pamper yourself: encircle your tub with lit votive candles, perfuse your bath with dark chocolate essence, and hop in!

Alternative coping strategy: don’t be a hermit.

Isolating yourself from mainstream celebrations may make you feel even more different from others, serve to intensify your unhappiness, and call attention to your conflict. So be a participant but choose your mindset. Who says you have to “live in the moment”? Live in another moment. Mentally return to another time,another place,another holiday season when you were happy. Deflect inappropriate probing questions with terse,curt replies and move on to converse with others. Who knows – you might end up having an unexpected,pleasant (and maybe even life-altering) conversation with someone. Only you know your mission – what consumes you. It is for you alone. Don’t renege on your resolve. You will realize your dream.

So smile while you’re makin’ it-
Laugh while you’re takin’ it-
Even though you’re fakin it-
Nobody’s gonna know.
Nobody’s gonna know.

(Alan Price – Poor People – O Lucky Man soundtrack – 1973)

IVF can increase a woman’s chances of a successful pregnancy and, depending upon the age of her eggs, the normalcy of the sperm, and the receptivity of her uterus percentages of success can far exceed those of the ideal couple in their 20s. With IVF treatment by “bumping up” the number of eggs available for fertilization, take-home-baby rates can, and do, approach 65-75%.

But the IVF process is replete with its own stressors. If you think about it ,all that with the good old-fashioned way of conception(traditionally) occurs behind closed doors or within the dark confines of the female pelvis is,with IVF, broken down, dissected, scrutinized and critiqued by every member of the IVF team. And then there are the injections (albeit with thin,humane needles), monitoring with blood tests and sonograms and, ultimately, sex in separate rooms! Egg retrieval is followed by anxiety over the box scores: how many decent blastocysts are there available for transfer or freeze and, ultimately, did it work.

Infertility is an emotional cauldron and the IVF process adds additional stress to the bubbling brew. How to cope? Dumping it all into the lap of one’s partner can be a recipe for disaster. A not uncommon consequence of this action is for one party to want to opt out of treatment and to express a wish for pregnancy to ‘happen naturally.” When I am confronted by couples in treatment discord such as this I gently point out that: 1) “Naturally” wasn’t working and that’s why they came to begin with.2) What’s common to everyone who comes for help is that no one wants to be here and that 3) When a couple “tries” to get pregnant relaxed spontaneity is a guise and either one or both parties is faking this behavior.

What to do with the stress? Some patients find help from support groups in which people undergoing the same treatments and who are experiencing the same feelings can feel understood. Resolve and the American Fertility Association are good organizations to contact for advice and to find local support groups. For those who prefer to cope privately I recommend Helen Adrienne’s book, On Fertile Ground. Healing Infertility. Helen is a psychotherapist with >30 years of experience in the field of infertility. Her timely book demonstrates her compassion, creativity, and insight into the psychological and social pain of infertility. It can be obtained through Helen’s website www.mind-body-unity.com.

Finally, I tell all my patients that,when they see a happy woman pushing a baby stroller,they have no idea what that person went through to have that baby. They have no idea how it happened. And, as for all those twins- they should just use their imagination! Success requires medical know-how and, often, aggressive treatment. Patience, time and love are essential. And no, you are not crazy!  Don’t give up your dream. Perseverance pays off…

So the love of your life came too late and your last period came too early. Pregnancy,then,must be out of the question? Not so. With the use of donor egg IVF your fantasy of family can be realized. Here how it works:

The intended mother,or recipient, is matched with a young (age 19 – 30),healthy “egg donor” whose physical characteristics and cultural background are similar to her own. Most egg donations are anonymous (donor and recipient never meet and the donor never learns if there is a pregnancy resulting from the donation) but designated donation between known parties can also be executed. Both donor and recipient are prescribed regimens of hormonal treatments: the donor’s to develop multiple eggs (usual yield 15 – 20), the recipient’s to prepare her endometrium, or uterine lining, to receive embryos created from the fertilization of the donated eggs with her partner’s sperm. The embryos,once created, are cultured and grown for five days. The goal (as with autologous IVF) is to have two well- expanded blastocyst-staged embryos to transfer to the uterus of the intended mother.Supernumary embryos of equal quality may be cryopreserved for future attempts to create or expand a family.

A patient will often ask if her uterus won’t “reject” embryos that are made with someone else’s eggs. Embryos, even if created with ones own eggs, are always “non-self”. The egg contributes only half of an embryo’s DNA – the sperm the remainder. The uterus is an immunoprivileged environment which, for the most part, “allows” these embryonic foreign bodies to implant, grow, thrive, and resist rejection.

Another oft-asked question concerns the preparation of the endometrium to receive embryos. Won’t the uterus “know” that the hormones that are prescribed for this purpose are exogenous drugs and not naturally occurring? Fortunately the uterus is not very discriminating. It does not “care” if the estrogen and progesterone required for endometrial development are secreted by a person’s ovaries or are adnministered via transdermal patch, tablet, cream, or vaginal suppository. And with donor egg pregnancies,just as with those that arise naturally, the placental pharmacy begins to function in the latter third of the first trimester and all hormone medications can then be stopped. Donor egg pregnancies then proceed just as and are indistinguishable from pregnancies conceived with a woman’s own eggs.

For patients the hardest part about donor IVF is deciding whether it is right for them. While participation in the program is undertaken with hopes and anticipation of the gains of pregnancy and parenthood it also signifies acknowledgement of the loss of a woman’s own reproductive potential. The mixed bag of emotions that surfaces when the use of donor eggs is being considered should be discussed with a patient’s physician, staff, or a skilled therapist. Once a couple has decided to go ahead they most often proceed with great excitement and anticipation. The eggs, once retrieved, are the patient’s and any pregnancy derived from these eggs is experienced exactly as would be a pregnancy generated from her own DNA. Nobody has ever reported an out-of-body experience carrying a pregnancy derived from donor eggs!

If a woman is healthy, of normal weight, and does not smoke pregnancy after menopause is a popular option for family building. How old is too old and at what age is pregnancy risky to a woman’s health? These are important questions that should be discussed at length between prospective donor egg recipients and their physicians. For the most part, however, recently menopausal women in their late 40s and early 50 are excellent candidates for donor egg IVF.
Who says you can’t have everything?

Once the sadness and anger over a failed IVF cycle have been addressed it is not uncommon for the disappointed couple to want to begin a new treatment cycle with the onset of the next “Day One”.In part this is a good thing: with the passage of time a woman’s eggs age and her chances of having a successful pregnancy diminish so waiting six months or a year to initiate a new cycle may considerably lower her chances for success. In addition studies have shown that embryo quality, implantation rate, and percentage of ongoing pregnancy are not compromised if IVF cycles are initiated back to back. Psychologically, “getting back on the horse” right away is purposeful, proactive, and, hopefully, productive.
Before beginning the next round of treatment it is essential that the couple consult with the physician to review, in detail, the previous failed cycle. Were there an adequate number of days of stimulation? Was follicular growth synchronous? Was the HCG trigger timed correctly? Was there anything that the physician would do differently on a subsequent cycle?
The lab data should be scrutinized as well: fertilization rate,embryo grades,timeliness of compaction, percentage of embryos reaching the blastocyst stage and the number of cells in the stem cell masses are some of the parameters assessed.
Once the clinical and laboratory aspects of a cycle have been reviewed a decision can be made as to whether another try might be more fruitful.

But how many cycles are appropriate? If IVF doesn’t work at what point should one stop cycling and discuss other options for parenthood? Too often patients get so caught up in the process that IVF becomes – well – like taking one’s chances at a slot machine: Let’s say that it takes 3 cherries to win the jackpot. You pull the handle -no cherries – so you try again: 1 cherry. You use another quarter and pull again: 2 cherries – and you get a small return of quarters. You have covered your “expenses” and have even made a few dollars’ profit. At this point it would be prudent to walk away with your cash but the last round with 2 cherries lures you into trying again. After all, 2 cherries is almost 3.
Not So. And like repeated pulls of the slot machine arm each cycle of IVF is an independent event and each sperm-egg combination is unique. Having a chemical pregnancy as a result of IVF is no better or “closer” to delivery than a complete failure of implantation. That said, a woman’s response to ovarian stimulation is pretty consistent cycle to cycle (at any one age) and if an ongoing pregnancy is not attained after two well-executed cycles another cycle of the same may just be a waste of money, time,and emotional energy. At this point swapping out eggs or sperm or both (ie donor gametes) or further investigating the uterus to make sure that it is a hospitable place for embryo development are options that should be given strong consideration.

 In the IVF lab fertilization of the eggs is the first but the easiest hurdle to overcome. If the sperm parameters meet acceptable standards then we allow the eggs to choose their mates. ICSI (intracytoplasmic sperm injection) is a laboratory intervention employed if there are few progressively motile normally shaped sperm to work with. With this technique individual sperm are selected, picked up with microinstruments, and injected into eggs that have been retrieved and prepared to receive them. Fertilization, either “natural” or assisted, occurs on “Day 0″. On “Day 1″, the following day, we see how many eggs have fertilized.The fertilized eggs (now called preembryos)  are then cultured and grown for 5-6 days during which time they navigate a genetic obstacle course. Those embryos that are genetically competant will make it to the blastocyst stage and, if they have  sufficient stem cell masses, will be appropriate for transfer to the uterus. As most sperm-egg combinations are not normal,having more eggs to fertilize (up to a point : 12-15 is a good yield) will increase the liklihood of ending up with a few embryos that can “go the distance”.With IVF it really is a numbers game and, in this game, the eggs and the sperm run the show.

So if we would do anything to achieve a healthy pregnancy but we can’t change the genetics of the “raw materials” what, exactly, can we do to improve upon nature? We can do an awful lot for male factor infertility: we can find and isolate the good sperm and make sure it gets where it needs to go. (For the most part normally shaped sperm contain normal DNA.) We can culture embryos to the blastocyst stage as our laboratory culture conditions simulate the hormonal and enzymatic environments of the fallopian tubes where embryo development usually occurs. In so doing we can effect embryo development for women with diseased or absent tubes and we can bipass the normal fallopian tube conduit whose function is to get blastocyst -stage embryos where they need to go. In addition, by creating more sperm-egg combinations in any one cycle we are taking a very inefficient process, human reproduction, and making it more efficient.

Special thanks to Meat Loaf for his invaluable assistance in the preparation of this post.

  Couples seeking assisted reproductive technologies must consider several important factors when comparing clinic success rates. The CDC has provided a guide for patients (http://www.cdc.gov/ART/ART2006/ifct.htm#Important Factors). Furthermore, reproductive medicine is renowned for the speed at which new methodology, technology, and drugs are incorporated into clinical treatment. Therefore, the success rates from two years ago are of limited value to the patient. Some clinics advertise more recent success rates, but these rates are unverified and should be interpreted with caution. So how do you determine your chances of success at a given clinic? The truth is you cannot. That’s why there is a disclaimer on every clinic-specific report stating that programs cannot be compared based on success rates.

  However, there is a way to generally compare programs using the SART clinic-specific report. The great equalizer in IVF is the use of donated eggs. Many of the confounding variables such as diagnosis, maternal age, egg number and quality are eliminated and the entire IVF process is optimized when eggs from a young donor are used. Therefore, the best way to compare programs is to compare the live birth rates for cycles in which donated eggs are used. This will give you a pretty good idea of the competency of the physicians and the quality of the laboratory.

  Beyond the SART statistics, there are several factors to look for when choosing an IVF program. One very important factor is the credentials, experience and personality of the physician. SART recommends that a board-certified or board-eligible Reproductive Endocrinologist (RE) act as the Medical Director of the IVF program. A board-certified RE has successfully completed a 2-3 year fellowship training program, a written examination and an oral examination. A board-eligible RE has completed the fellowship training program, but has not yet completed the written and/or the oral examinations. Some doctors who are board-certified in obstetrics and gynecology also offer infertility treatments, but they have not completed subspecialty training in infertility. In addition to formal training, the number of years of experience the doctor has will also play a part. An RE just out a fellowship program may be up to date in the theoretical aspects of infertility treatment, but lack hands on experience. On the other hand, an RE who has been in practice many years (and remained up to date) likely possesses the knowledge and experience to suggest the best treatment option for you. Finally, the doctor’s personality will also play a role in your choice of programs. During your initial consult and in subsequent treatment, you should feel free to ask as many questions as you like and be satisfied with the depth of the answers you receive. A doctor that appears hurried or dismisses your questions with quick answers can leave you anxious and stressed. The more information you have, the more relaxed you will be throughout your treatment.

  The IVF laboratory will also play a very significant role in determining your success, but assessing the quality of the laboratory can be tricky. The quality of the laboratory will depend on the credentials and experience of the laboratory staff and the effectiveness of the laboratory procedures and technology employed. According to the CDC guidelines, the Director on an IVF laboratory must be a doctoral level scientist (Ph.D.) or physician, board-certified in clinical embryology. However, the law does not require that the Director perform the procedures or, for that matter, be physically present in the laboratory. In most large programs, the Director provides administrative oversight and does not actively participate in the day-to-day operation of the laboratory. This means that, in many cases, the IVF procedures (insemination, ICSI, embryo culture, assisted hatching, embryo biopsy, etc) are being performed by embryologists. This is not exactly a comforting thought, so you should inquire as to who performs the laboratory procedures and what are their credentials and experience before choosing a program.
  The technology utilized by the laboratory is very important. There is no standard IVF method and every IVF laboratory has its own protocols and methods. Some protocols work better than others, but most protocols work reasonably well. Beware of programs offering brand new (and untested) technology, as you may end up being an unwitting research subject. You should also be aware that IVF technology has developed rapidly during the past few years and so programs that have not changed their technology to keep up may not have the highest success rates. Recent advances in the composition of culture medium now make it possible to routinely culture embryos to the blastocyst stage of development prior to embryo transfer. There are several advantages to transferring blastocyst stage embryos. Although programs differ in deciding which patients should have a blastocyst stage embryo transfer, any program that discourages transferring the embryos at the blastocyst stage should probably be avoided.
  What should you do if you were referred to or choose and program and now you are not happy with the treatment you are receiving? Simple – change programs! Having established a relationship with a doctor, some people find it very difficult sever that bond of trust. However, one of the biggest mistakes a patient can make is staying with a program that is not meeting their needs. If you are unhappy with your treatment, seek a second opinion or change to a program that meets your needs. When seeking a second opinion, it is important to obtain all the pertinent medical records, lab reports and embryology records.
  When choosing an IVF program, the SART-verified success rates, the credentials of the physicians and laboratory staff and the quality of the laboratory should weigh significantly in your decision.