A study in the August 2010 issue of Fertility & Sterility looks at the time it took to establish a pregnancy that led to a live birth and cost-effectiveness of either conventional treatment with three cycles of clomiphene citrate CC/IUI, three cycles of gonadotropins FSH/IUI, and up to six cycles of IVF or an accelerated treatment that omitted the three cycles of FSH/IUI.

An increased rate of pregnancy was observed in the accelerated arm compared with the conventional arm. Median time to pregnancy was 8 and 11 months in the accelerated and conventional arms, respectively. Per cycle pregnancy rates for CC/IUI, FSH/IUI, and IVF were 7.6%, 9.8%, and 30.7%, respectively. Average charges per delivery were lower in the accelerated arm compared to conventional treatment. The observed incremental difference was a savings of $2,624 per couple for accelerated treatment.

In my experience many couples are bypassing the option of FSH/IUI, not only because of the increased time and expense to success, but also because IVF provides more control over high-order multiple pregnancies as we transfer fewer embryos.

Arthur L. Wisot, M. D.

A. No more than the average person.

Q. Then why are FDA inspectors spending their time in IVF centers monitoring egg donation records while members of the public are dying from salmonella infection?

A. It's because a well-meaning Congress assigned the FDA to monitor the infectious disease screening of egg donors, taking hard-working FDA inspectors who are trained to inspect food out of the henhouse and putting them into our offices. We have had FDA inspectors in our offices for a week on several occasions making sure all the t's are crossed and i's dotted instead of monitoring food and drugs. FDA are the initials for the Food and Drug Administration and what egg donors have to do with food or drugs is beyond me.

In fact, in an article in todays's Los Angeles Times, only half of the scientists surveyed at the federal agency responsible for monitoring the safety of the nation's egg supply have full confidence that their organization adequately protects consumers from food-borne illness in eggs — and that was before the recent salmonella outbreak.

I say let's get the FDA inspectors out of the fertility centers and back into the henhouses to really help protect the public.

Arthur L. Wisot, M. D.
 

But which is most effective?  A study in the July 2010 edition of Fertility and Sterility compared  metformin, clomiphene, metformin and clomiphene and weight loss. The clinical pregnancy rate was 12.2% in clomiphene group, 14.4% in metformin group, 14.8% in clomiphene + metformin group, and 20% in lifestyle modification group. The lifestyle modification group achieved a significant reduction in waist circumference, total androgen, and lipid profile, not only improving their fertility, but general health as well.

The problem is that very few patients are able to lose enough weight to achieve a pregnancy with lifestyle modification alone and most need to also use the drugs. But if they can achieve it, their fertility and general health will benefit substantially.

When a couple ends a cycle with poor quality embryos the focus is usually on the eggs. But now there is more focus on sperm quality as a cause of poor embryo quality, specifically the degree of DNA fragmentation in the sperm. In an article in the July 2010 issue of Fertility & Sterility  the percentage of normal sperm with fragmented DNA (normal SFD) was correlated with embryo quality and pregnancy outcomes.

A highly statistically significant negative correlation was found between the percentage of normal sperm with fragmented DNA (SFD) and embryo quality. When the percentage of SFD was less than 17.6 %, the likelihood of pregnancy was 3.5 times higher. The authors concluded that the DNA fragmentation of morphologically normal sperm negatively impacts embryo quality and probability of pregnancy in ICSI cycles.

This is an issue that we have been looking at for some time, performing a Sperm Chromatin Structure Assay (SCSA) when couples have experienced repeated IVF failure, especially associated with poor embryo quality. Strategies to reduce DNA fragmentation include lifestyle changes when appropriate, antioxidant vitamins, shorter intervals of ejaculation prior to the IVF specimen and in rare cases, obtaining sperm by testicular biopsy (TESE).

A survey in the July 2010 issue of Fertility & Sterility examined the choices made by parients at one fertility center. Of 149 patients from Washington University in St. Louis, 59% donated them to scientific research, 38% discarded, and 3% donated to a known or anonymous person/couple for attempted pregnancy. There was no significant difference in the choice selected between patients who achieved a pregnancy with delivery compared with those who did not.  In addition, the patient's age at retrieval and at the time of disposition as well as the total time in storage was not significantly different between patients electing to discard and those donating to research.

My experience at Reproductive Partners is that most couples avoid making this difficult decision and just keep their embryos frozen indefinitely. For highly successful couples the optiion of donating to another couple who has exhausted their options is a a way of giving something back when they have been so fortunate. But, as we can all understand, it can be difficult to have one's biologic offspring out there without having any knowledge or control of their future.

A few years ago there was an estimate of 400,000 frozen embryos in IVF centers throughout the United States, lending credability to the difficuty in making a decision to release them.

Dr. Wisot was interviewed about the dangers of pregnancy after breast cancer, an aspect of the story they completely ignored in the article. The most important point he made to them was the option now for women to preserve their fertility using egg freezing prior to starting chemotherapy, an aspect of the story they also ignored. According to the story Christina Applegate did not undergo chemotherapy or radiation so she could pregnant, instead choosing to have a bilateral mastectomy which would not affect her fertility.

Egg freezing is now a very realistic option for women choosing to delay having a family as well as women surviving cancer.

Dr. Wisot has been quoted in many media outlets including celebrity magazines such as People Magazine, US Weekly and Life & Style.

The authors surveyed 4976 clinical pregnancies from one large IVF center and found ninety-eight cases of monozygotic twins (MZTs) were diagnosed after first-trimester ultrasound evaluation (2% incidence). In naturally conceived pregnancies the incidence is about 0.25-0.5%. 

The incidence in women transfering embryos from their own eggs was 1.7% but was 3.3% with donor eggs; however, younger women (<35 years old) using their own eggs displayed a similar rate (3.1%) to women using donor eggs.

Eighty MZTs occurred after fresh day-5 transfer; only 14 followed fresh day-3 transfer (2.6% vs. 1.2%). The MZT incidence in day-3 transfers without assisted hatching was not different from those with hatching (1.3% vs. 1.1%). In addition, MZT incidence did not differ significantly whether or not ICSI was performed (2.4% vs. 2.0%). Four MZTs occurred after frozen-thawed embryo transfer (0.8% incidence).

The good news is that ninety-five percent of all placental arrangements were confirmed as having two amniotic sacs on obstetric ultrasounds, making them safer pregnancies than when both babies are in the same amniotic sac.

The take-home message is that this is a good reason for young women and those using eggs from a young donor to seriously consider elective single embryo transfer (eSET) so if a set of identical twins does occur and the other embryo implants one does not have to deal with a triplet pregnancy.

In response to a question about how this reflects on the fertility industry Dr. Wisot replied, "Most people understand that these are the actions of somebody who is way, way out of bounds and doesn't represent the mainstream of fertility treatment," said Dr. Arthur Wisot, fertility specialist with Reproductive Partners in Redondo Beach . "He has been shunned by the medical community as much as you can possibly shun somebody….He's totally out there, flying solo."
 

Cystic fibrosis carrier screening, chromosome analyses, and hemoglobin evaluations are performed on the majority of sperm donor applicants. Tay-Sachs disease carrier screening is performed on most donors with Jewish heritage but there is significant variation in screening for other disorders .

Since the screening of sperm donors is not usually complete, we recommend that all of our patients do a fairly comprehensive screening of themselves or their partner (if they are using their partner's sperm) for recessive genetic diseases. We use Counsyl screening which screens over 100 recessive diseases using a saliva specimen. Of course there are still some genetic diseases not covered such as the ones that are dominant and others that are not in Counsyl's panel. One still needs to rely on family history and ethnicity to determine if any other testing is needed.

We are fortunate that technology exists to determine if anyone is a carrier of an abnormal gene since we can now employ preimplantation genetic diagnosis (PGD) for single gene defects to detect whether an embryo is affected before transfer, thus reducing the chance of a child with the genetic disease without needing to consider termination of a pregnancy.