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Sex selection

Blastocyst transfer

Integrins and implantation defects

Antiphopholipid syndrome and coagulation defects

Ovarian tissue freezing

Co-Culture


Home : Contents : Selected IVF Topics of Current Interest

Selected IVF Topics of Current Interest

Sex Selection

Throughout history couples have wanted to be able to select the sex of their unborn child. Recent surveys in America show that couples interested in sex selection are interested in it primarily to balance the sex of children in their family. Couples wish to experience the excitement of raising both a boy and a girl child.

Throughout time there have been many approaches to sex selection. Until recently, these have been based on either simple-minded or sexist approaches to sperm. My favorite technique in the history of this subject is based on the belief that boy sperm originated in the right testicle and girl sperm originated in the left testicle. This belief persisted for hundreds of years. If one wanted a boy child, all that one would have to do is to tie off the left testicle.

In the 1950's there were very popular books that described how to select a particular sex for your child with prescriptions for the how, why and when of intercourse. More recent approaches have utilized sperm processing. The basis for some of these approaches was the belief that boy sperm (being intrinsically superior) swim faster than girl sperm. Millions of dollars have been spent by patients to obtain some of these sperm processing techniques.

With sophisticated DNA testing it is clear that none of these older techniques are actually able to differentiate boy, or Y chromosome containing sperm and girl, or X chromosome containing sperm. The difference in mass of an X and Y sperm is approximately 3%. There are both subtle and non-subtle differences in the shape of sperm not related to the sex of the sperm. These significantly effect both the mass of the sperm and the way that that sperm swims much more than the small difference in mass due to the difference in the X and Y chromosome. Although controlled trials for sperm selection have always been a study that medicine is capable of doing, to my knowledge, no one has ever undertaken a truly controlled trial comparing these older methods of sperm selection.

There is now one technique that has been shown to be effective in selecting X and Y bearing sperm. The technique uses a fluorescent stain on the sperm and the sperm are separated using a flow cytometer (sometimes referred to as a cell sorter). This technique of cell sorting is available through IVF And Genetics Institute in Fairfax, Virginia (703-876-3897). It is still an experimental procedure, but preliminary data suggests that it is particularly good at selecting X bearing, or female, sperm. Unfortunately, because of technical reasons even if one is starting with a very good specimen, only a few sperm are able to be selected. Because of the small number of sperm selected the variant of IVF known as ICSI, where sperm are injected directly into eggs, is required for a high probability of conception.

This procedure can be performed at Infertility Solutions, P.C. using IVF And Genetics Institute to perform the sperm sorting procedure. The husband would produce a specimen for us here. We would freeze it and ship it to IVF and Genetics Institute. They would then re-freeze it and ship it back to us. We would then undertake ICSI and defrost the sperm that have been sorted, and use them in the procedure. The sorting procedure increases the cost of the IVF/ICSI procedure by about one-third. Since the procedure is still experimental, IVF And Genetics Institute has a separate consent form that would have to be signed by the couple requesting this procedure.

More recently another technique for sex selection has been clinically available, namely PGD. It's accuracy is theoretically 100%. PGD involves creating embryos with IVF, removing a cell from the embryo and testing that cell to see if it is from a male or female embryo. Embryos of the desired sex can then be transferred.  (Couples may cryo-preserve, donate or discard their left over embryos.)

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Blastocyst Transfer

Blastocysts are 5 or 6 day old embryos that have divided into enough cells to be ready to hatch out of their zona pellucidas. Blastocysts are generally more likely to grow into viable pregnancies then are 4 or 8 celled embryos. Some (but not all) problems with embryos that prevent their developing into viable pregnancies will also prevent them from developing into blastocysts. Recently developed techniques enable us to better assess even day one embryos and thus some of the advantages of blastocyst culture can be achieved with other methods which can be used by a larger subgroup of patients. New culture media have recently been developed that enable us to develop a larger proportion of embryos into embryos in laboratory culture than previously. Some programs are hopeful that the use of day 5 blastocyst transfer will enable them to enhance their pregnancy rates while decreasing their high order multiple birth rates. Data on the value of blastocyst transfer has been mixed.  Presently, in good prognosis patients, it can be used to limit the number of embryos transferred. However, for such patients, it does not appear to reduce the multiple gestation rate, although it does reduce the incidence of triplets.

In the best of situations, only a subset of embryos will develop into blastocysts. Many of those embryos which did not develop into blastocysts, if transferred into the uterus earlier, may have had the potential to become pregnancies. Patient age, response to the ovulation induction, and embryo quality are all variables that are correlated to getting pregnant without blastocyst transfer. Patients with a good response to the ovulation induction and good embryo quality are the patients for whom the data most clearly suggests that blastocyst transfer may be of benefit. The benefit of blastocyst transfer in patients with a poorer prognosis for traditional IVF has yet to be demonstrated. It has also been shown that blastocyst culture cannot completely select against chromosomally abnormal embryos (which would have been an important benefit).

Most programs that do a lot of blastocyst transfer use it for highly selected patients. Such patients generally do well, in terms of achieving pregnancy, no matter what technique is used. It does not seem likely that blastocyst transfer in itself enhances the pregnancy rate.  It does appear to be true that by the faster growing embryos, one can safely decrease the number of embryos transferred on day 3 without a drop in pregnancy rates.  A similar benefit may be obtained by looking at the entire growth pattern of a person's embryos rather than only growth at one point in time.

We feel that blastocyst transfer plays an important role in IVF. For good prognosis patients, it can be used to eliminate the risk of high order multiple births. Twins remain a significant problem. Blastocyst transfer is also necessary when embryo biopsy will be used to screen for genetic abnormalities (PGD).

We currently utilize blastocyst transfer selected patients.  We more highly value evaluating the entire pattern of embryo development in deciding on day of transfer and number of embryos to recommend.  Over time the proportion patients undergoing blastocyst transfer has waxed and waned in this program.

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Integrins and Implantation Defects

Integrins are proteins that are produced by the endometrium around the time of implantation. They are thought to play an important role in enabling implantation to occur.

Many studies have shown that women with fluid-filled closed tubes (closed hydrosalpinx), have half the pregnancy rate of other women with other types of tubal disease. Recently there have been two papers which have shown that removing those tubes surgically enhances the pregnancy rate with IVF. Bruce Lessey's group has shown that women with fluid-filled hydrosalpinx do not produce integrins as well as normal women. They have also shown that removing the fallopian tubes enables the uterus to produce these integrins.

There may also be other gynecological conditions that cause impaired integrin expression. Endometriosis may cause infertility on this basis in some patients. Testing for integrins is now a clinically available test. The primary lies in how one will use the information once it is obtained.  We evaluate integrin expression in a limited number of patients.  Generally we look at integrin expression when we suspect an implantation defect that we can not easily treat.

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Anti-phospholipid Syndrome and Coagulation Defects

We feel that some of our patient population has infertility in part on an autoimmune basis. Presently there is not good way to determine this. There have been publications suggesting that it is worthwhile to measure antiphospholipid antibodies prior to undertaking IVF. These antibodies are directed against the developing placenta. Although there is data supporting this approach, it is very limited. Recently several good large negative studies have been published (in the area of infertility, but not recurrent pregnancy loss). If anti-phospholipid antibodies are found and thought to be significant, then the treatment of choice is heparin and aspirin. If the patient has a history of recurrent pregnancy loss, we also look for coagulation defects such as factor V abnormalities. Such defects may lead to abnormal clotting occurring within the placenta.

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Cryopreservation of Ovarian Tissue

Ovarian tissue freezing is a process in which very small pieces of the ovary are frozen and preserved in liquid nitrogen. Ovarian tissue freezing is an experimental procedure that may enable patients to preserve fertility prior to chemotherapy, radiotherapy, or prior to removal of their ovaries by surgery. Only small pieces of ovary may be preserved in this way, but if the patient is young, those small pieces may contain thousands of eggs. The process of freezing such small pieces of tissue is relatively well established. However, the process of utilizing these small pieces of tissue to achieve pregnancy in humans has not yet been worked out. Pregnancies have been achieved in sheep, but those techniques may not be suitable for humans. The best that can be said at this time, is that there is a great deal of optimism among reproductive biologists that the details of how to use this tissue to achieve pregnancy in humans will eventually be worked out.

The process involves taking small biopsies or pieces of the ovary. The size of these pieces is about the size of a grain of rice. The biopsies are placed in cryoprotective media (special fluid) and frozen with a controlled rate freezer in liquid nitrogen. The biopsies are then stored in liquid nitrogen at a temperature of -190C. This temperature is below the minimum temperature required for chemical reactions to take place, and theoretically there is no limit on how long the tissue can be stored.

Alternatives to this procedure which preserve fertility, are to undergo an IVF cycle in which as many eggs as possible are obtained. The eggs need to be fertilized and then frozen as embryos. Technology to freeze unfertilized eggs and achieve pregnancy will shortly be widely available, but is currently considered an experimental procedure. Another alternative is to utilize donor eggs at the time that pregnancy is desired.

This procedure is viewed as experimental.

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Co-culture

The FDA has written to IVF programs about their concerns with the practice of growing non-human animal cells together with human embryos. This practice is often referred to as co-culture. The idea behind it was that the animal cells would produce chemicals that would help the human embryos to grow. Because of concerns with exposing human embryos to possible unknown infections (including the human version of Mad Cow Disease), co-culture with foreign cells is, for practical purposes, prohibited.

Infertility Solutions has NEVER used co-culture of human embryos with foreign cells.