IVF In Vitro Fertilization
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IVF - In Vitro Fertilization

The story of in vitro fertilization - IVF is fascinating. Lesley Brown and her husband, John, had been unable to conceive for nine years. Lesley was diagnosed with bilateral fallopian tube obstruction. In 1976, she was referred to Dr. Patrick Steptoe. He recommended that she try a new experimental procedure that would bypass the fallopian tubes blockage completely.

Lesley underwent a laparoscopy whereby a single mature egg was aspirated from one of her ovaries. John's sperm was added to the egg in the laboratory under the direction of Robert G. Edwards. A few days later a developing embryo was placed into Lesley's uterus.Louise Brown - The world's first IVF baby

At 11:47 p.m. July 25, 1978, Louise Joy Brown was delivered by cesarean section. She weighed five pounds 12 ounces and had blonde hair and blue eyes.

Louise has just celebrated her 30th birthday. The world celebrated the 30th anniversary of a new era. The era of extra corporeal assisted reproduction. History will regard that moment 30 years ago with as much awe and importance as the first moon landing.
On December 20th, 2006, Louise gave birth to her own child, Cameron John Mullinder. She conceived without fertility treatment of any kind on the six month that she and her husband tried. The delivery was by cesarean section since the baby was breech.


Before Louise there was... the rabbits

In 1891, Walter Heape (1855-1929), a professor and physician at the University of Cambridge, England, who had been conducting research on reproduction in numerous animal species, reported the first known case of embryo transplantation. Working with two species of rabbits, he flushed embryos from the oviducts (rabbit fallopian tubes) of one breed (Angora) and placed them into the uterus of a recently mated Belgian hare. In the resulting litter, there were 4 Belgians and 2 Angoras. Heape proved that it was possible to take preimplantation embryos and transfer them to a gestational carrier without affecting their development.

As a result of this work, many scientists became interested in culturing eggs and embryos in the laboratory. Gregory Pincus and colleagues were the first to show how eggs of various animals would undergo maturation if released from their follicle and cultured in a laboratory. In 1939, he reported that human eggs would mature in the laboratory within 12 hours. It was not until 1959, however, that M.C. Chang reported, in the journal Nature, the first unequivocal case of a live birth following egg fertilization in the lab, true in vitro fertilization and subsequent embryo transfer, to the uterus.

Robert Edwards gets involved

Bob Edwards became interested in working with humans in 1958. His first challenge was that he found that human eggs did not mature in vitro (in the laboratory) when released from the follicle as Pincus had reported in 1939. Using ovarian slices provided by Dr. Molly Rose, his wife's obstetrician, Dr. Edwards worked for two years trying to induce human egg maturation without success. As it turned out, human maturation took twice as long as what had been reported by Pincus. This error wasted two years. Eventually, each stage of human egg maturation was timed and in vitro fertilization of human eggs was achieved.

Patrick Steptoe arrives

In 1968, Dr Edwards phoned Patrick Steptoe after reading of his groundbreaking work with laparoscopy. They agreed to team up to try to accomplish human in vitro fertilization. Dr. Steptoe would aspirate the egg from the follicle (egg retrieval) via laparoscopy and Dr. Edwards would fertilize it in vitro and culture the embryo. Dr. Steptoe would then transfer the embryo back to the uterus (embryo transfer). A clinic was set up in a small hospital outside of Cambridge. Amidst a flood on controversy from the press, religious authorities and even other physicians and scientists, the stage was set for the first human in vitro fertilization pregnancy.

Medication problems

Initially, patients were stimulated with fertility medications in order to help with obtaining eggs. However, several patients developed severe luteal phase deficiency. Luteal phase deficiency is a problem that occurs when there is inadequate progesterone support of the uterine lining after ovulation or egg retrieval. The decision was made to supplement the patients with additional progesterone. Initially, daily injections of progesterone in oil was chosen but due to the problems inherent with the use of intramuscular progesterone (which persist until this day), they switched to a synthetic progesterone that could be given every five days. Sadly, this decision resulted in failure over the course of the next two years due to the abortion inducing properties of the synthetic progesterone.

Diagnosing pregnancy was more difficult due to the lack at that time of sensitive pregnancy tests. Despite this limitation, a few embryo transfers resulted in a brief rise in a serum pregnancy test. These early pregnancies were designated as "biochemical pregnancies" since the blood test was the only proof of their existence.

IVF Pregnancy

Drs. Steptoe and Edwards published a report in 1976 in the medical journal Lancet. A human embryo at the late morulae /early blastocyst stage was transferred into the uterus and resulted in a clinical pregnancy. Unfortunately, the result was an ectopic pregnancy (tubal pregnancy) and had to be removed.

Finally, they decided to abandon the use of fertility medications and try aspirating a single egg in a natural menstrual cycle. In addition, they returned the embryo to the uterus earlier at the eight cell stage in the hopes that this would compensate for perhaps inadequate culture condition in vitro. On their second attempt, Louise Brown was conceived.

IVF Spreads around the world

In June 1980, an Australian team led by Alan Trounson, produced that country’s first (and the world’s third) IVF baby. In the United States, Howard and Georgianna Jones’ IVF program in Norfolk, VA produced this country’s first IVF baby, born December 28, 1981. This also marked the return of injectable fertility drug to help stimulate an IVF pregnancy. Since the introduction of IVF, it is estimated that there have been millions IVF babies born worldwide.  IVF babies now make up a measurable percentage of the total births n developed countries. Some of these children, now grown to adulthood, have begun to have their own children, IVF's second generation.

Milestones in the history of in-vitro fertilization

May 1981
First report of using ultrasound for percutaneous oocyte retrieval instead of laparoscopy
March 1983
First egg donation pregnancy
1984
First delivery of an infant from egg donation
January 1984
First surrogate embryo transfer baby born in California
January 1984
First donor embryo baby born in Melbourne
March 1984
First baby born from thaw of frozen embryos in Melbourne
June 1984
First report using transvaginal ultrasound guidance for egg retrieval
January 1986
First report using Lupron to prevent premature ovulation
October 1987
First report using ultrasound for embryo transfer
March 1988
Death of Patrick Steptoe
1990
First pregnancies reported after preimplantation genetic diagnosis - PGD by our laboratory. Also first reported case of sex selection (gender selection) in IVF
1991
First report using assisted hatching of the zona pellucida to improve pregnancy rates
July 1992
First report of pregnancies and deliveries using intracytoplasmic sperm injection (ICSI)
1999
Recombinant gonadotropins become available for clinical use


In 2007, over 100,000 IVF cycles were performed in the United States alone.

Understanding the steps for performing IVF - In Vitro Fertilization

IVF Drug treatment

Drugs to prevent Premature ovulation

  • Cetrotide and Antagon in IVF
    Cetrotide and Antagon are the primary medications that help prevent premature ovulation.

  • Lupron treatment in IVF
    An older method for preventing ovulation

  • Drugs to stimulate the ovaries to produce multiple eggs

  • Fertility Drugs for Stimulation of Egg Development
    Fertility drugs are used to stimulate the development of multiple eggs during in vitro fertilization (IVF)

  • hCG Trigger
    A final injection of hCG prepares for retrieval

  • Drugs to assist development of the uterine lining

  • Progesterone supplementation
    Progesterone is administered to help sustain the uterine lining (endometrium).

  • Egg removal, Fertilization, Growing Embryos and Placement in the uterus

  • Egg (Oocyte) Retrieval
    Removal of the eggs (oocytes) from the ovary.

  • What happens in the IVF laboratory?
    Learn about methods of fertilization, embryo culture and development.

  • Embryo transfer
    The embryos are placed into the uterus.

  • Overview of the IVF process - What can you expect?

  • IVF from start to finish
    What are the average numbers than IVF patients can expect? If you are going through an IVF cycle - read this!!!
  • What issues are important if I get pregnant from an IVF cycle? 

  • IVF birth defects
    Is IVF associated with a greater incidence of birth defects or not? If you are going through an IVF cycle - read this!!!
  • IVF Pregnancy Screening
    Many women who have IVF are older and therefore at greater risk for babies with chromosome abnormalities. These women may have screening tests for abnormalities performed. The results should be interpreted with caution, however. Read why here. If you are pregnant from an IVF cycle - read this!!!

  • Frequently asked questions (FAQ) about IVF

    • Is bedrest important after an IVF embryo transfer?
    No. A number of studies have looked at IVF pregnancy rates in women who were instructed to rest after an embryo transfer and compared them to pregnancy rates in women who were not instructed to rest. The conclusion of every study that has looked at this was that bedrest after embryo transfer does not improves the chances for an IVF pregnancy. 
    Articles to read about bedrest in IVF:

    Recent in-vitro fertilization (IVF) developments

     

    07/19/2008 PGD does not cause birth defects in children  

    07/17/2008 IVF does not cause developmental problems in babies  

    03/14/2008 New IVF sperm separation study shows promising results  

    03/08/2008 Long term freezing does not harm frozen embryos  

    02/09/2008 New IVF acupuncture study 

    11/23/2007 IVF complications explained  

    070/7/2007 IVF study: No benefit to using Embryoglue  

    03/16/2007 Anti-Mullerian Hormone (AMH) predicts IVF success
    02/27/2007 Surgery for ovarian cysts may reduce ovarian reserve and lower success with IVF
    02/27/2007 Using egg, donation, a 67 year old woman conceived and delivered twins
    02/23/2007 A recent study failed to find a benefit for assisted hatching during IVF
    10/16/2006 Infection with HPV was associated with lower IVF pregnancy rates
    09/23/2005 Egg donors are not at increased risk for infertility themselves
    09/14/2005 Study: No difference between types of natural vaginal progesterone during IVF
    09/14/2005 IVF Children are Taller and Have Better Cholesterol Profiles than Other Children
    07/01/2005 AZH - Assisted Hatching - Does Not Help Endometriosis Patients During IVF
    05/17/2005 Stress Does Not Decrease IVF Success
    05/17/2005 Egg Donation May complicate Pregnancy
    04/08/2005 Smoking Reduces IVF pregnancy rates
    03/06/2005 IVF Success rates do not depend on bedrest
    02/23/2005 New FDA regulations will hurt egg and embryo donation
    02/21/2005 Americans Support PGD
    02/08/2005 Study: Blastocyst transfer for repeated IVF failures
    02/05/2005 Single embryo transfer in IVF may be the sane as a transfer of two embryos
    01/31/2005 Study suggests IVF babies are at higher risk for birth defects
    01/26/2005 PGD is used to prevent Rh sensitization
    01/17/2005 Sixty seven year old woman delivers twins using In vitro fertilization - IVF and egg donation
    01/08/2005 In vitro fertilization - IVF - success rates decline with age? Duhh!
    01/07/2005 ICSI does not increase miscarriage risk
    01/06/2005 Health risks of children born from in vitro fertilization (IVF)?
    01/05/2005 Bedrest after in vitro fertilization (IVF) not necessary

    Additional in-vitro fertilization (IVF) topics

    In vitro egg maturation enables egg retreval and embryo transfer without the use of fertility medications
    Endometriosis and IVF Endometriosis is associated with infertility but IVF is a good treatment to overcome it.
    Frozen Embryo Transfer
    Minimal stimulation IVF is a topic that a lot of people are talking about these days. What is it and how effective is it?
    IVF What can the average patient expect?
    IVF Implantation Failure
    Single embryo transfer in IVF
    Intracytoplasmic sperm injection - ICSI
    Blastocyst
    Preimplantation genetic diagnosis PGD
    Understanding IVF Pregnancy Rates
    Acupuncture in IVF
    IVF Connections


    Egg Donation Learn about performing in vitro fertilization using donated eggs.
    Egg Donor Application If you are interested in becoming an egg donor for one of our patients, download this application (Requires Adobe Acrobat), fill it out and mail back to the office.

    Last Updated ( Friday, 19 June 2009 )