The International Council on Infertility Information Dissemination, Inc

A new way to track ovulation at home

MFB Fertility, LLC Develops Only In-Home Test to Detect Progesterone

 

Research has shown that couples get pregnant faster when they know when exactly when ovulation takes place. Fertility monitors and ovulation predictor kits allow couples to track estrogen and luteinizing hormone (LH) levels from home. However, until now, there were no tests available to track progesterone.

 

 

Erie, CO, March 23, 2016 --(PR.com)-- The process of ovulation involves three main hormones that change during the monthly menstrual cycle. The first is estrogen, this hormone is essential for an egg to mature. Second is luteinizing hormone (LH). A surge in this hormone allows the egg to mature and be released from the ovary (also known as ovulation). Finally, there is progesterone. This hormone is produced in the ovary after the mature egg is released and acts to prepare the uterus for embryo implantation. If pregnancy occurs, progesterone levels will remain high throughout the pregnancy to help support fetal growth. Fertility monitors and ovulation predictor kits allow couples to track estrogen and LH levels from home. However, until now, there were no tests available to track progesterone. MFB Fertility, LLC has developed a test that measures the presence of progesterone in urine, which helps a woman "double check" that they have ovulated. Read more at www.mfbfertility.com or click here 

Dramatic and Tragic Decline in Intercountry Adoption Numbers Continues

FOR IMMEDIATE RELEASE

Media Contact:                                                

Lauren Koch
(703) 299-6633

lkoch@adoptioncouncil.org

Dramatic and Tragic Decline in Intercountry Adoption Numbers Continues

April 1, 2015 – Alexandria, VA – The U.S. Department of State has released its FY 2014 Annual Report on Intercountry Adoption. According to the report, American families adopted 6,441 foreign-born children in 2014, a more than 9% decline from 2013’s 7,094 adoptions, and a 74% decline over the last 10 years since 2004 when there were 22,991 foreign-born children adopted. This is the lowest number of adoptions since 1982.

In 2008, the U.S. implemented the Hague Adoption Convention on the Protection of Children and Co-operation in Respect of Inter-Country Adoption (The Hague Convention), an international agreement established to provide universal protections and regulations for the adoption of children and promote cooperation among signatories of the agreement.

At the time of implementation, many advocates, including National Council For Adoption (NCFA), believed the Hague Convention had the potential to increase opportunities for orphaned and abandoned children around the world to find safe, permanent, loving families through intercountry adoption. NCFA supported the Hague Convention’s signing and implementation in the hope that it would provide new opportunities and hope for children living without the care of a family. We believed the U.S. Central Authority would be advocates to help move children ethically and without undue delay into the care of the permanent families that are so crucial to their development. We believed the U.S. Central Authority, Department of State’s Office of Children’s Issues, would serve as a proactive support to adoption – working with other nations to find ways to work together to bring children in need out of the dangers of institutionalization, homelessness, or other horrors and into families where they could pursue their full potential.

“At a time when the orphan population is growing and there are many thousands of willing, waiting adoptive parents it is heartbreaking that intercountry adoption has faced such drastic decline,” notes Chuck Johnson, president and CEO of National Council For Adoption. “Although we believe the Hague has brought positive ethical reform and uniform practice, we are extremely disappointed in the lack of advocacy. We believe that the Hague Convention still holds great potential, but it has been inappropriately implemented.”

The Office of Children’s Issues in Consular Affairs does not advocate for the betterment of children, they serve only regulatory functions. We believe that a new office for the Central Authority is necessary to see the need for advocacy met. Advocacy would include seeking out ways to educate, partner with, and support countries willing and desiring to partner with the U.S. in their children’s best interest through intercountry adoption.  We believe that moving the authority to manage intercountry adoption to an alternate office with the mandate not only to maintain an ethical process, but also to pursue the best interests of children is essential to the future of intercountry adoption and the many thousands of children who can find their way to the safety and wholeness of home through it.

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ABOUT NATIONAL COUNCIL FOR ADOPTION

Founded in 1980, National Council For Adoption (NCFA) is a global adoption advocacy nonprofit that promotes a culture of adoption through education, research, legislative action, and collaboration. As the authoritative voice for adoption, NCFA’s areas of focus include domestic infant adoption, adoption and permanency outcomes for youth in foster care, and intercountry adoption. Passionately committed to the belief that every child deserves to thrive in a nurturing, permanent family, NCFA serves children, birth parents, adopted individuals, adoptive families, and adoption professionals. In addition, we work tirelessly to educate U.S. and foreign government officials and policymakers, members of the media, and all those in the general public with an interest in adoption.

For more information, visit www.AdoptionCouncil.org.

 

New Study: IVF success rates can be excellent for high responding women when using a Lupron trigger

Infertility Specialist Richard Sherbahn Presents New Research Study at the American Society for Reproductive Medicine Annual Meeting

Results of a new research study, conducted by Dr. Sherbahn and Dr. Catenacci of Advanced Fertility Center of Chicago, show that proper use of a Lupron trigger can result in high IVF success rates, and no ovarian hyperstimulation.

"IVF success rates can be excellent for high responding women when using a Lupron trigger."

Press Release: Gurnee, IL (PRWEB) January 15, 2015 --- Dr. Sherbahn's Professional Member profile and  Biography

Board-certified fertility specialist Richard Sherbahn, MD recently presented research on the use of a Lupron trigger (agonist trigger) to prevent ovarian hyperstimulation in women with a high response to ovarian stimulation for IVF at the annual meeting of the American Society for Reproductive Medicine in Honolulu, Hawaii. The study, conducted by Dr. Sherbahn and Dr. Catenacci of Advanced Fertility Center of Chicago, looked at IVF live birth success rates, pregnancy loss rates, and ovarian hyperstimulation syndrome (OHSS) occurrence rates in high responders that had a pure Lupron trigger vs. a dual trigger with Lupron and a small dose of HCG.

Included in the study were 135 women under the age of 38, all using their own eggs for in-vitro fertilization (IVF). They each either received a pure Lupron trigger or a Lupron trigger plus a small dose of HCG (1500-2000 units), between November 2011 and July 2013. Patients were separated into 2 groups based on their trigger injections (pure agonist trigger vs dual trigger). Intensive support was given in the luteal phase using intramuscular progesterone and oral or transdermal estradiol.

The mean number of eggs retrieved, miscarriage rates, and the rate of development of ovarian hyperstimulation syndrome were not significantly different between the pure Lupron trigger group and the dual trigger group. The live birth rate per egg retrieval was 52.6% in the pure agonist trigger group, while the dual trigger group rate was 64.4%. The difference was not statistically significant. There was a trend for higher pregnancy loss rates in the pure agonist group, but it was not statistically significant either.

The pure Lupron trigger group was then split into 2 groups according to the peak estradiol level - under or over 4000 pg/ml. The IVF live birth rate was significantly higher (p<0.05) in the group with peak estradiol levels greater than 4000 pg/ml (42.2% vs. 67.7%).

“Published studies on Lupron triggers, and other agonist drug triggers, have shown inconsistent results. We believe that, in the studies with poor IVF success rates, the patients were not given enough estrogen and progesterone support in the luteal phase and early pregnancy. We believe the luteal support needs to be aggressive, and must be continued into early pregnancy, until the placenta makes enough hormones to support the pregnancy,” explained Dr. Sherbahn.

The results of the study showed that live birth rates with IVF, using a pure agonist trigger, can be very high when intensive luteal support is given. Also, success rates using a pure Lupron trigger are significantly higher when the peak estradiol level is above 4000 pg/ml. Therefore, if the peak estradiol level is below 4000 pg/ml, a dual trigger with a low dose of 1500 IU of HCG should be considered.

“We believe that the Lupron trigger is a vital tool that has been available to IVF doctors for the last several years for reducing the occurrence of ovarian hyperstimulation – particularly in women with polycystic ovarian syndrome, PCOS. Before the Lupron trigger was available, there were significantly more cases of ovarian hyperstimulation syndrome, which is always uncomfortable for the woman, and in rare cases can result in severe medical complications,” said Sherbahn. Proper use of pure agonist triggers can result in excellent IVF success rates, and no ovarian hyperstimulation, or rare hyperstimulation cases with a dual trigger.

About The Advanced Fertility Center of Chicago

The Advanced Fertility Center of Chicago, with offices in Gurnee and Crystal Lake, Ill., offers advanced reproductive technology services such as in-vitro fertilization (IVF), intracytoplasmic sperm injection, preimplantation genetic diagnosis, egg freezing and egg donation.

The Center specializes in individualized care, and has IVF success rates and egg donation success rates that are well above national averages.

The Center’s web site, http://www.advancedfertility.com, offers more than 300 articles on fertility issues and IVF. To schedule an appointment, call 847.662.1818.

 

Unrestrained Danger - Virginia Schools May be Hurting Children

For Immediate Release:   
Contact: Colleen Miller
August 11, 2014  
disAbility law Center of Virginia
(804) 225-2042

Virginia Schools May be Hurting Children

 

            Children in Virginia’s public schools may be subjected to long periods of seclusion and restraint with virtually no oversight or regulation by the State Department of Education, according to a report released today by the disAbility Law Center of Virginia.    The dLCV collected policies and procedures from almost all school districts in Virginia and reviewed them for the presence of protections for children with disabilities.

            128 of Virginia’s 133 school districts provided information for the report.  The results were discouraging:  32 school districts reported that they do not have any procedures that restrict a teacher’s ability to restrain or seclude a child. 83 school districts provided procedures that fail to meet the suggested “guidelines” developed by the Virginia Department of Education.  No public school produced standards that would meet the requirements set for private schools in Virginia.  In Virginia’s public schools, a child may be restrained for an unlimited amount of time, and the school faces no oversight or regulation.  Schools do not even have to notify the parents when a restraint has been used.

            “Nothing in Virginia code or regulations prohibits a school from putting a child in dangerous restraints, nothing limits how long a child may be left in seclusion, no rules control whether or not a school can lock a child in a closet all day long.  For most children, these practices would be considered abusive, but when the child has a disability, many public schools allow the practice,” said Colleen Miller, the Executive Director of the disAbility Law Center of Virginia.

            The report, Unrestrained Danger: Seclusion and Restraint in Virginia’s Public Schools, issued today urges the Commonwealth to create uniform and consistent policies that are evidence-based, focused on positive behavioral supports, data-driven, trauma-informed, and person-centered.  In addition, the Commonwealth should limit the use of restraint and seclusion in public schools as a last resort -- only when there is an immediate and significant risk of physical injury and only when less restrictive interventions have failed.  Statewide policies must prohibit the most dangerous practices, including mechanical restraints and prone restraints.

 

            The disAbility law Center of Virginia is a newly created nonprofit organization that serves as the state’s designated protection and advocacy system.  The dLCV’s mission is to combat abuse and neglect, to promote the civil rights of people with disabilities, and to encourage that people with disabilities have choice, independence and inclusion in all aspects of their lives.  The dLCV advocates for all people with disabilities to be free from abuse, neglect and discrimination.

            The Unrestrained Danger report and supporting detailed analysis, Seclusion and Restraint in Virginia’s Public Schools: Investigative Study of Policies and Procedures to Protect Students, can be found at www.dlcv.org.

 

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Effects of BPA and Phthalates on Conception and Pregnancy

October 14 , 2013

by: ASRM Office of Public Affairs
Published in ASRM Press Release

HIGHLIGHTS FROM THE INTERNATIONAL FEDERATION OF FERTILITY SOCIETIES 21st WORLD CONGRESS ON FERTILITY AND STERILITY AND THE 69th ANNUAL MEETING OF THE AMERICAN SOCIETY FOR REPRODUCTIVE MEDICINE

Boston, MA-  Researchers presenting at the conjoint meeting of the International Federation of Fertility Societies and the American Society for Reproductive Medicine have identified specific effects of bisphenol A (BPA) and phthalates on human reproduction. 

These chemicals are used in the manufacture of plastics and other products, accumulate in the environment and human tissues and are known to be endocrine disruptors.  While evidence is growing that BPA and phthalates influence the success of couples undergoing IVF, less is known about how these chemicals affect couples who are presumed fertile, who are trying to conceive, and how they affect a woman’s ability to sustain a pregnancy. 

In one study, examining BPA and phthalate levels in 501 couples trying to become pregnant, researchers from the National Institute of Child Health and Human Development, Texas A&M Rural School of Public Health, and the New York State Department of Public Health found that phthalate concentrations found in the male partners, but not the females, may be associated with approximately a 20% decline in fecundity.

Couples discontinuing contraception in order to become pregnant were recruited between 2005 and 2009.  They were interviewed at the outset, examined, and all individuals provided urine samples for measuring their BPA and phthalate levels.  In addition, the couples kept journals on intercourse and lifestyle and the women recorded their menstrual cycles and pregnancy test results.

The researchers found that higher BPA concentrations in the female partner did not lead to decreased fecundity and that, in fact, higher concentrations of a certain phthalate were associated with a shorter time to pregnancy.  In the male partners, concentrations of other phthalate chemicals were associated with diminished fecundity and longer time to pregnancy.

O-2  Bisphenol A, Phthalates and Couple Fecundity, The Life Study GM Buck
Louis et al   
 


In another study, researchers from Stanford University, the University of California San Francisco and the University of Missouri found that women with levels of BPA in the highest quartile are at significantly increased risk of having a miscarriage. 

They recruited 114 women having an early pregnancy test at four to five weeks gestation.  The enrollees gave blood to be stored. This was later tested for BPA levels in the women who had given birth and in the women who had had a first trimester miscarriage with testing for chromosomal abnormalities.  Serum BPA concentration levels were ranked in quartiles and the researchers calculated the relative risk of miscarriage for women in each quartile of serum BPA concentration.

Women who had had a miscarriage had higher average BPA levels than those who had live births and the risk of miscarriage increased with increasing levels of BPA in the maternal serum- whether the fetus was chromosomally normal or not.

O-61     Maternal Serum Bisphenol-A (BPA) Level Is Positively Associated with Miscarriage Risk 
RB Lathi et al 

ASRM President Linda Giudice, MD, PhD observed, “Many studies on environmental contaminants’ impact on reproductive capacity have been focused on infertility patients and it is clear that high levels of exposure affect them negatively.  These studies extend our observations to the general population and show that these chemicals are a cause for concern to all of us.”


Also of interest:

Chinese scientists have found that high BPA levels in the follicular fluid of polycystic ovarian syndrome (PCOS) patients may inhibit the activity of a gene in granulosa cells, interrupting the conversion of androgen to estrogen and causing an abnormal accumulation of androgen hormones.

O-42  Bisphenol A (BPA) Induces Abnormal Androgen Accumulation Via Androgen-Androgen Receptor (AR) Mediated CYP19A1 Transcription Inhibition in Granulosa Cells (GC’s)
Pan et al 

Representing more than 50 fertility societies from around the globe, the International Federation of Fertility Societies (IFFS) is the world’s principal international fertility organization. The IFFS was founded in 1951, and held its first congress in New York in 1953. The IFFS mission is to stimulate basic and clinical research, disseminate education and encourage superior clinical care of patients in infertility and reproductive medicine. Website: http://www.iffs-reproduction.org/ 

The American Society for Reproductive Medicine, founded in 1944, is an organization of more than 7,000 physicians, researchers, nurses, technicians and other professionals dedicated to advancing knowledge and expertise in reproductive biology.  Affiliated societies include the Society for Assisted Reproductive Technology, the Society for Male Reproduction and Urology, the Society for Reproductive Endocrinology and Infertility, the Society of Reproductive Surgeons and the Society of Reproductive Biologists and Technologists.


For more information on these press releases, contact:

J. Benjamin Younger Office of Public Affairs
409 12th Street SW, Suite 203
Washington, DC 20024-2188
Tel: (202) 863-2494/Fax: (202) 484-4039

Contact

Eleanor Nicoll
Phone: 240-274-2209
Email: enicoll@asrm-dc.org

 

Press Release: A JOURNALIST’S GUIDE TO ADOPTION

For Immediate Release: March 8, 2005

For More Information Contact: Kathryn Creedy

Institute for Adoption Information

802-442-7135, kcreedy@adoptioninformationinstitute.org

IAI PROVIDES UPDATES TO A JOURNALIST’S GUIDE TO ADOPTION

 

Bennington, VT, -- In its third update to A Journalist’s Guide to Adoption, the first, unbiased adoption research portal designed for and by journalists, Institute of Adoption Information has expanded coverage of the all facets of adoption issues, including children in foster care, embryo adoption, adoption ethics, safe havens and open records. It also is the only publication that puts adoption into context with the modern family. IAI, which designs guides for professionals who encounter adoption in their work, links the "JGuide," published in 2003, to the most current information on adoption now on the web at www.adoptioninformationinstitute.org.

"With this tool, agencies, child welfare officials and adoption support organizations can introduce themselves to their local media and work with them to enhance both the understanding of adoption and the quality of reporting on adoption," said IAI Executive Director Kathryn Creedy. "In any week, there are hundreds of adoption stories whether it is a legislative battle to open adoption records, the homecoming of a long-awaited child, the meeting of adoptees and their birth families, corrupt adoption practices, or an in-depth report on what makes a family. Despite the frequency with which these stories appear, adoption is little understood, and coverage often inadvertently perpetuates myths and stereotypes. This guide has become the prime adoption portal helping journalists understand adoption."

A Journalist’s Guide to Adoption gives journalists a basic familiarity with a variety of adoption-related subjects and provides links to the best unbiased resources and research. In addition, it includes a list of reliable experts and links to organizations working on specific agendas. It helps journalists:

Understand the adoption process and ethical adoption practices;

Provide balanced information that does not perpetuate myths and stereotypes;

Use more accurate and appropriate language;

Determine when adoption is germane to coverage;

Put adoptive and birth families into context with the changing modern family; and

Understand how adoption holds lessons for other non-traditional families especially for the million-plus children resulting from assisted reproduction and surrogacy.

The guide recounts how adoption is changing the modern family as well as the serious social implications of not understanding adoption including the crisis in foster care, teen parenting, and infant homicide. It also addresses the implications of baby-abandonment laws and explores how public prejudice toward adoption hampers adoption planning for children who still await permanent homes.

The project includes contributions from Adam Pertman, author of Adoption Nation and executive director of the Evan B. Donaldson Adoption Institute. It has also been reviewed for accuracy by some of the top adoption professionals including Ada White, director of adoptions, Child Welfare League of America; Brenda Romanchik, executive director of Insight, a birth parent advocacy group; Marilyn Waugh, president of American Adoption Congress, one of the largest adoptee resources in the country; Marley Greiner of Bastard Nation, The Adoption Rights Organization; and the National Adoption Information Clearing House.

The guide is the third in a series of guides published by IAI. An Educator’s Guide to Adoption, designed for teachers, was published in 1999 and A Guide to Adoption for Health Care & Counseling Professionals, designed for the pre-natal medical and counseling communities, was published in January. IAI plans several more guides for both consumers and professionals.

IAI is a nationwide, non-profit organization of adoptees, birth parents, adoptive parents and adoption professionals who have united to enhance the understanding of adoption through education.

###

 

 

Kathryn B. Creedy

Executive Director

Institute for Adoption Information

PO Box 4405

Bennington, VT 05201

802-442-7135

kcreedy@adoptioninformationinstitute.org

www.adoptioninformationinstitute.org

 

GIVF's MicroSort: Technology separates the boys from the girls by Keith Blauer, M.D. and David Karabinus, Ph.D., H.C.L.D.

GIVF's MicroSort
Technology separates the boys from the girls 

by Keith Blauer, M.D. and David Karabinus, Ph.D., H.C.L.D. 

 

Many of us know someone who would desperately like to have a girl. Or a boy. Perhaps a couple has several children of one gender already and would like to have another child --- but would only consider doing so if the 50/50 odds could be shifted in favor of the other gender. Or, perhaps a couple is seeking infertility treatment, already has one child, and would prefer that the next child is the other gender. Yet another couple may want to avoid passing a gender-lined genetic disease to their child.

If a scientifically proven method of gender selection existed, these individuals might consider using it. The Genetics & IVF Institute (GIVF) started investigating gender selection technology in the early 1990s. And now the FDA has approved a clinical trial for GIVF's preconception gender selection process, called MicroSort.

When a sperm with a Y chromosome fertilizes an egg, it makes a boy. When an X chromosome bearing sperm fertilizes, it makes a girl. Any given sperm sample contains an even (50/50) amount of X (female) and Y (male) bearing sperm. MicroSort uses a machine called a flow cytometer to sort sperm such that the sorted sperm population is enriched in either X (female) or Y (male) bearing sperm. Once the sperm has been sorted, it can be used with assisted reproductive techniques to achieve a pregnancy. Since it is in a clinical trial, patients must be fully informed of the potential risks and benefits.

 

How does the technology work? 
The separation of male and female sperm is based on the measurable difference in the quantity of genetic material (DNA) they contain. The sperm absorbs a dye, which attaches temporarily to the DNA, or genetic material, inside the individual sperm. When exposed to laser light, the dye fluoresces. Since the X chromosome is larger than the Y, there is more DNA for the dye to attach to and, consequently, the sperm with the X chromosomes will fluoresce more brightly than those with Y chromosomes. The flow cytometer is able to pick up these differences in brightness and separate the sperm as they move through the machine one at a time.

Currently, MicroSort sperm sorting technology improves the chance of a female pregnancy to 89.5 percent after sorting. For a male, MicroSort has improved the chance to 73.6 percent.

 

How does a couple use the sorted sperm to become pregnant? 
The most common method uses the sorted sperm with intrauterine insemination (IUI). The woman is monitored carefully to establish the time of ovulation. Some of this monitoring can occur with her local physician and/or the use of ovulation predictor kits. Insemination is performed very close to the time of ovulation. On the day of ovulation the husband produces a sperm sample, the sperm are sorted for the desired gender, and the insemination with the sorted sperm occurs later that same day.

At the current time, couples must come to the clinic in Fairfax, VA to have their IUI procedures performed with fresh specimens. It is hoped that more U.S. locations will be available soon, making the technology more accessible.

For patients who need additional assistance achieving pregnancy, sorted sperm can be used with IVF. Sperm can be sent frozen, then sorted and returned to a local IVF center, allowing the couple to have IVF close to home. Please refer to the MicroSort website www.microsort.com for a full listing of physicians (collaborators) participating as part of the clinical trial.

MicroSort has accomplished more than 350 pregnancies. Based on the data so far, the likelihood of having a normal, healthy baby is not different from that of the general population.

 

Who qualifies for gender selection by MicroSort? 
Currently couples must be in one of two categories. A couple with a history of an X-linked disease, where the woman is a known carrier, may qualify for free treatment with MicroSort. Examples of such disorders include hemophilia and Duchenne muscular dystrophy. Other couples can choose to use MicroSort for family balancing. Family balancing couples must be married, the wife must be between ages 18 and 39, and they must have at least one child and be selecting for the less represented gender of children in their family.

 

Is MicroSort here to stay? 
MicroSort is the only scientifically verifiable method of pre-conception gender selection. It is showing positive results after more than 350 pregnancies. For couples today who are considering options for having a family, especially those with chromosome-linked concerns, MicroSort gender selection is of serious interest. As the science continues to improve and centers open in other locations, we expect that MicroSort will become a routine part of family planning.

 

PGD: The Next Step in Pregnancy Enhancement and Disease Prevention or the Search for the Holy Grail of Infertility Treatment by Carlene W. Elsner, M.D., Z. Peter Nagy, M.D., Ph.D, and Amy E. Jones, M.S.

PGD:  The Next Step in Pregnancy Enhancement and Disease Prevention or the Search for the Holy Grail of Infertility Treatment

Carlene W. Elsner, M.D., Z. Peter Nagy, M.D., Ph.D, and Amy E. Jones, M.S.

 

Preimplantion Genetic Diagnosis (PGD) makes it possible to detect genetic abnormalities in the embryo prior to embryo transfer. This technology offers huge potential for improvement in outcomes of IVF treatment, including improved pregnancy rates, reduced miscarriage rates, and avoidance of an ever expanding list of genetic abnormalities. With each passing year, more can be learned about an embryo and its ultimate development potential from a single cell.

 

BACKGROUND

Before PGD was available, chromosomal abnormalities in the conceptus could not be detected until the pregnancy was already established. Prenatal diagnosis of chromosomal abnormalities in the fetus prior to birth has been in use for many years. It is currently recommended for all pregnant women over the age of 35, because the risk of maternal age related genetic abnormalities begins to rise at this age. Fetal cells are obtained for culture either by chorionic villus sampling or amniocentesis. These procedures are typically performed in the late 1st trimester or in the early 2nd trimester of pregnancy. A relatively large number of fetal cells can be safely obtained at this time and tested to determine a full karyotype (testing of all 23 chromosome pairs) of the fetus as well as detection of single gene defects and translocations is possible. If an abnormality is detected, abortion can then be performed to terminate the pregnancy and avoid the birth of an abnormal child. However, couples who want children, find the concept of abortion emotionally difficult if not ethically impossible.

With PGD, there is the possibility to detect many, but not all, genetic abnormalities in the embryo before the pregnancy is established. This helps to avoid the need for many therapeutic abortions and reduces the risk of maternal age related miscarriage in older women. As a woman ages, the likelihood of becoming pregnant in any given cycle declines and the miscarriage rate rises. Every time a pregnancy is terminated or miscarried, the woman loses 3-6 months of precious time needed to complete her family plans. Older women cannot afford that lost time. By age 40, at least 50% of a woman’s embryos will be chromosomally abnormal (Munne et al.). With the use of PGD, abnormal embryos are eliminated from the group of embryos selected for replacement into the uterus or cryopreservation, so these pregnancies are never established. Clearly, PGD is a giant step forward in our ability to help women have healthy babies.

PGD can also be used to detect many genetic diseases that are a result of single gene defects occurring in some families. In these families, the risk of having an abnormal child is not related to maternal age, but to which genes are inherited from the mother and father. Usually, in these cases, both parents have one normal gene and one abnormal recessive gene. Each parent is healthy. For the disease to occur, the child must inherit the abnormal gene from both parents. PGD can detect which embryos have the disease (two abnormal genes), which are normal (two normal genes), and which are carriers (one normal and one abnormal gene) like the parents. This information can be used in the selection of which embryos to replace in the mother’s uterus and which are appropriate for cryopreservation. PGD offers the potential of eliminating these diseases altogether.

In addition to women with known genetic diseases in the family and older women at risk for maternal age related genetic abnormalities, there are two other groups who may benefit from PGD. Seventy percent of embryos may be abnormal in women under 35 who have a history of repeated unexplained miscarriage (Simon et al.). A similar percentage of abnormal embryos (70% has also been reported in a group of women with multiple failed IVF cycles (Pehlivan et al.). PGD should be discussed with both of these groups of women before additional IVF treatments are performed, so that the best embryos can be selected for transfer.

 

TECHNIQUES OF BIOPSY

The development of microtechnology that makes it possible to test for chromosomes or single genes in a single cell has made PGD a reality. Testing can be performed either on the 1st and 2nd polar bodies of the egg or on a single cell extracted from the embryo at the 6-8 cell stage (day 3 of embryonic life) or on the embryo at the blastocyst stage (day 5 of embryonic life).

Polar body biopsy involves the analysis of genetic material extruded from the egg during meiosis. The 1stpolar body is formed with maturation of the egg, and the 2nd is formed during the process of fertilization. Both of these structures contain chromosomes that have been excluded from the embryo during its formation and, therefore, may be analyzed without risking damage to the embryo itself. Then, the chromosomal makeup of the egg may be determined by inference.

Embryo biopsy involves the removal of a single cell from an embryo after fertilization at the 6-8 cell stage of development, just after compaction (the process by which the cells of the embryo attach to one another) has occurred. Biopsy can be done at this time without damage to the embryo because one single cell can be removed through a small opening created in the zona pellucida without fear that the rest of the embryo might escape through the opening. Analysis of this cell can then give information on not only the maternal, but also the paternal genetic contribution to the embryo. Blastocyst biopsy is a possible alternative to day 3 embryo biopsy. It is not used very widely because it is technically more challenging and also because it may not always provide an interpretable result. Both polar body biopsy and embryo biopsy are in current usage.

 

TECHNIQUES OF ANALYSIS

Two techniques are available to test the genetic material (DNA) obtained in the biopsy. They cannot both be done on the same sample obtained from a single cell, so a choice must be made. Fluorescent in situ hybridization (FISH) is used to test for an abnormal number of chromosomes within the embryonic cell. Polymerase chain reaction (PCR) technology can detect an abnormality within a single gene on a chromosome pair, but PCR does not test for extra or absent chromosomes as does FISH. Some diseases are caused by aneuploidy (extra or absent chromosomes) and others are caused by single gene defects.

 A normal human cell contains 23 chromosome pairs. Fluorescent in situ hybridization (FISH) is used to test for aneuploidy. It involves attaching color coded fluorescent tags to chromosome pairs from a single cell removed from an embryo and fixed on a slide. When examined microscopically, two fluorescent signals indicate the normal diploid state. Three signals indicate trisomy, and one signal, monosomy for the particular chromosome studied. Currently, in our laboratory, testing is available for 9 chromosomes, X, Y, 13, 15, 16, 17, 18, 21, and 22. This technology detects Down’s syndrome (trisomy 21), Turner’s syndrome (45XO), Klinefelter’s syndrome (47XXY), and a myriad of other abnormalities involving extra or absent chromosomes.

When the abnormality to be detected is limited to a single abnormal gene on a single chromosomal pair, polymerase chain reaction (PCR) technology is used to amplify segments of DNA to make possible the detection of defects using the minute amount of DNA in a single cell. Some of these abnormal genes contain extra copies of a 3 base sequence (triplet repeat) that make them bigger than the normal gene, i.e. Fragile X. The number of these repeated sequences is variable, so each abnormality is unique. Other abnormal genes may have a portion of the gene deleted, i.e. cystic fibrosis. Therefore each test must be tailored to fit the couple and the exact abnormality to be detected. The test sample DNA from the embryo is then run along with DNA from each parent to detect the presence or absence of the defective gene. This technology is used for the detection of

normal, carrier, and affected embryos for diseases like Tay Sach’s disease, cystic fibrosis, Duchenne’s muscular dystrophy, Fragile X and an ever expanding list of diseases caused by single gene defects. Genetic matching (HLA typing) can be combined with PCR in families with children with Fanconi’s anemia to detect embryos that are both normal and an HLA match for the affected child so, after the birth of the normal child, stem cells from the normal child can be used to save the life of the sick child.

In both of these techniques, embryos are biopsied on day 3. The cell removed is then tested. Testing can be very time consuming and may require up to two days to complete. Normal embryos are replaced in the woman’s uterus on the afternoon of day 4 or the morning of day 5. If a pregnancy is established, chorionic villus sampling or amniocentesis is still recommended because it is not possible to detect all chromosomal abnormalities with current technology.

 

THE FUTURE

Microarray technology currently under development offers the opportunity to test for all 23 chromosome pairs at once. Additionally, it provides the possibility to screen the complete genetic information of the embryo, facilitating the prevention of genetically inheritable diseases. This exciting new technology is not yet sensitive enough for use with the minute amounts of DNA in a single cell, but research continues in this area. When microarray technology can be adapted for use in single cells, it may represent the next major breakthrough in PGD.

 

Carlene W. Elsner, M.D. is a reproductive endocrinologist at Reproductive Biology  Associates in Atlanta Georgia.
Phone: 404-843-3064 or Toll Free 1-888-RBA-4IVF

Email: rba-online@rba-online.com

Website: http://www.rba-online.com

 

Z. Peter Nagy, M.D., Ph.D. is the scientific and laboratory director and Amy E. Jones M.S. is the laboratory supervisor at Reproductive Biology Associates.

 

REFERENCES

Munne, S., Alikani, M., Tomkin, G., Grifo, J., and Cohen, J.. Embryo morphology, developmental rates, and maternal age are correlated with chromosomal abnormalities. Fertil. Steril. 64[2], 382-391. 1995.

 

Pehlivan, T., Rubio, C., Rodrigo, L., Romero, J., Remohi, J., Simon, C., and Pellicier, A..Impact of preimplantion genetic diagnosis on IVF outcome in implantation failure patients. Reprod. Bio. Online. 6[2], 232-237. 2003.

 

Rubio, C., Simon, C., Vidal, F., Rodrigo, L., Pehlivan T., Remohi, J., and Pellicer, A.. Chromosomal abnormalities and embryo development in recurrent miscarriage couples.

Hum. Reprod. 18[1], 182-188. 2003.    

 

Infertility and Multiple Pregnancy: Can you have too much of a good thing? by Serena Chen, M.D.

Infertility and Multiple Pregnancy: 
Can you have too much of a good thing? 
by Serena Chen, M.D.

In general, the best way to reduce multiple births is to transfer only single embryos. In order to do that without dramatically lowering the overall pregnancy rate, implantation rates need to be increased. Implantation rate is the potential of a single embryo to result in a pregnancy and is calculated by taking the total number of gestational sacs divided by the total number of embryos replaced. Implantation rate is always lower than the pregnancy rate because the vast majority of IVF procedures involve the transfer of more than one embryo. The higher the implantation rate, the lower the number of embryos needed to achieve pregnancy, and the lower the multiple birth rate.

Improvements in various techniques used in the laboratory have led to gradually improving pregnancy rates across the country. Improved techniques of embryo culture, assisted hatching and fragment removal are being used more widely. As embryologists gain experience, implantation rates have improved. Again, improvements in implantation rates will ultimately allow physicians to replace fewer and fewer embryos, maintain or improve the overall pregnancy rate and someday, eliminate the risk of high order multiple pregnancy.

 

EMBRYO FREEZING
Cryopreservation or freezing of embryos is another technique that can be used to reduce multiple births. Cryopreservation is widely available and can help decrease the pressure to transfer large numbers of embryos by allowing a couple to freeze extra embryos for use at a later date. The disadvantages of cryopreservation are that some embryos will not survive the freeze-thaw process and previously frozen embryos may have less pregnancy potential than "fresh" embryos. However, there does not appear to be any increase in the rate of birth defects or miscarriages in pregnancies conceived using frozen-thawed embryos. As this technology continues to improve, with better freeze-thaw survival rates and better pregnancy rates, it will become a more powerful tool to help reduce multiple births.

 

PREIMPLANTATION GENETIC DIAGNOSIS (PGD)
Preimplantation genetic diagnosis (PGD), or the genetic analysis of embryos prior to transfer into the body is an exciting new technology that could help reduce multiple births. PGD can be used to look for chromosomal aneuploidy (abnormal numbers of chromosomes) in the embryo. This condition can lead to infertility, miscarriages and birth defects (an extra chromosome 21 causes Down's Syndrome). As a woman gets older, the chance that her embryos are chromosomally abnormal increases dramatically. In older women, the ability of the embryologist to select the embryos most likely to result in a pregnancy decreases markedly. This occurs because a higher proportion of the embryos are chromosomally abnormal and because most chromosomal abnormalities do not cause any changes in the embryos appearance. So a very high quality embryo can be very abnormal genetically. Because of the higher rate of chromosomal abnormalites, the implantation rate of the embryos decreases. By using PGD to select the chromosomally normal embryos, the implantation rate of the embryos that are selected is increased. The higher the implantation rate, the lower the number of embryos needed to achieve pregnancy and the lower the multiple birth rate. At this time, PGD can analyze only a limited number of chromosomes and only a few centers worldwide have significant experience in this technique. However, studies performed at Saint Barnabas have already demonstrated that PGD can improve pregnancy rates in women over 35, and dramatically lower the miscarriage rates. Ultimately, as the technique improves, PGD may allow us to offer all patients a single embryo transfer, eliminating the multiple pregnancy problem without sacrificing a high pregnancy rate.

 

CONCLUSION
Despite what many infertile couples think, it is possible to have too much of a good thing. Multiple pregnancies involve reward and risk. High order multiple pregnancy can result in serious complications for both the mother and the babies. There are various techniques available to try and minimize these risks. Couples should discuss these techniques with their doctor to decide how or whether to use them in their individual treatment plan.

 

Serena Chen, M.D. is Director, Division of Reproductive Endocrine Department of Obstetrics and Gynecology Saint Barnabas Medical Center and the Director, Ovum Donation Institute for Reproductive Medicine and Science at Saint Barnabas East Wing Suite 403 94 Old Short Hills Road, Livingston, NJ 07039
Tel 973 322 8286. Email Dr. Chen

 

Pregnancy and Multiple Gestation Rates after Transfer of Two Versus Three Blastocysts

Article Title: "Two-blastocyst transfer has similar pregnancy rates and a decreased multiple gestation rate compared with three-blastocyst transfer"

Authors and Affiliations: Amin A. Milki, Jeffrey D. Fisch, and Barry Behr, Department of Gynecology and Obstetrics, Stanford University School of Medicine.

 

Summarized by Christine M. Schroeder, Ph.D.

In IVF, transfer of more embryos is often associated with a higher chance of pregnancy. However, transferring more embryos also confers an elevated risk of multiple pregnancy. Blastocyst transfer may provide at least a partial solution to this dilemma, because blastocysts have higher implantation rates than day 3 embryos. Because of the higher implantation rates, not as many blastocysts have to be transferred back to the uterus in order to achieve satisfactory pregnancy rates.

The authors of the current study began offering fresh blastocyst transfer routinely to patients who are at risk for multiple gestations in January 1998. All patients were advised to transfer only two blastocysts; however, patients willing to undergo selective reduction were allowed to transfer up to three blastocysts. Despite this fairly conservative policy, the clinic noticed that the proportion of multiple pregnancies at their clinic increased. Due to the fact that there was little information on the issue of multiple pregnancy and the number of blastocysts transferred, the authors decided to compare the two and three day blastocyst transfers.

The study was retrospective, which means that the researchers went back and reviewed the cases of women who had undergone two- and three-blastocyst transfers; in other words, patients were not randomly assigned to type of transfer. Twenty-nine patients had two blastocysts transferred (the 2B group) and 24 had three transferred (the 3B group). Despite the fact that they had not been randomly assigned to treatment, the 2B and 3B groups were similar in age (35.1 years average), the number of previous IVF cycles, the number of oocytes retrieved, the number of embryos on day 3, and the number of blastocysts that ultimately developed. Patients with embryos fertilized conventionally and via ICSI were both included in the study.

Analysis of the results indicated that:

  • The 2B and 3B groups both had implantation rates of 47 percent.
  • Pregnancy was defined as two positive rising hCG tests taken two days apart. The pregnancy rate in the 2B group was 73 percent and in the 3B group, it was 76 percent.
  • Viable pregnancy was defined as visualized fetal cardiac activity at seven and nine weeks gestation. The viable pregnancy rate in the 2B group was 58 percent, and the viable pregnancy rate in the 3B group was 62 percent.
  • The twin pregnancy rate in the 2B group was 39 percent, and the twin pregnancy rate in the 3B group was 50 percent
  • The triplet pregnancy rate in the 2B group was zero percent, and the triplet pregnancy rate in the 3B group was 29 percent

 

Thus, over three fourths of the pregnancies in the 3B group - 79 percent - were multiple gestations, compared to 39 percent in the 2B group. Additionally, none of the multiple gestations in the 2B group were triplet gestations, whereas 36 percent of the 3B group pregnancies were triplet gestations.

Thus, two blastocyst transfers sharply reduce the risk of multiple gestation, with no compromise in overall pregnancy rate. Based on these results, the researchers strongly recommend that patients be encouraged to transfer only two blastocysts.

 

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