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IVF

In Vitro Fertilization (IVF) is the process by which oocytes (eggs) are fertilized by sperm in a laboratory and the resulting embryo(s) are transferred back into the uterus at a time which is associated with optimal implantation.  ICSI (Intracytoplasmic Sperm Injection) entails selecting a single sperm and injecting each oocyte singly.  This is beneficial for couples with diagnoses complicated by severe male factor.  The following describes each step of the process:

1.  Pre-IVF evaluation/Consult:  Once a couple chooses to pursue IVF, we perform what is called a mock embryo transfer and uterine cavity evaluation.  This is a process whereby our patient comes to the office with a full bladder.  This allows for an easier embryo transfer given that the full bladder helps to straighten the uterine angle.  We are also able to better visualize the uterus since we look transabdominally and ultrasound visualization is optimized when transmitting through a fluid medium.  The mock transfer takes approximately five minutes and its importance is in determining the correct catheter and path to facilitate an easy, straightforward and painless embryo transfer.  Most women describe it as a speculum exam with a full bladder.     

We also perform an in office hysteroscopy which is a procedure in which a small camera is placed through the cervix and we examine the uterine cavity on a high definition monitor.  It does not require anesthesia and may be associated only with mild cramps.  The objective is to make absolutely certain that there is nothing that may negatively impact embryo implantation.

In addition, we review the stimulation calendar with the couple at this visit.  This is a detailed spreadsheet of the cycle each day and the schedule and dosing of medications.  It is extremely simple to follow and we are accessible 24 hours a day, 7 days a week and instruct and encourage patients to call with any question, no matter how minor they feel it may be.  We also review how to give the medications and what to expect.  

2.  Ovarian Stimulation and Follicular Monitoring:  Stimulation for egg retrieval usually takes between 8 and 12 days.  In this interval of time most will require approximately 3-4 ultrasounds that are designed to measure the follicles.  Follicles are cystic areas within the ovaries that increase in size over the stimulation process.  Once the follicles achieve the optimal size to yield the greatest number of mature eggs, we time an hCG trigger shot.  hCG ensures that we will retrieve oocytes that are mature enough to fertilize.  The retrieval procedure is performed approximately 35 hours after the hCG shot and timed specifically to produce the highest quality, mature oocytes which are retrieved before ovulation would occur.

The stimulation process, whether for ovulation therapy or IVF/ICSI is designed to “rescue” eggs that would normally be lost.  By timing the start of stimulation, we are able to stimulate few to many eggs depending on the treatment desired.

3.  Egg/Oocyte Retrieval:  The egg retrieval is timed based on the hCG injection as mentioned above.  It takes approximately 10 minutes and is performed under heavy sedation.  Patients are asleep during this procedure.  A transvaginal ultrasound is performed with a guide.  A needle is passed into each follicle and the fluid along with the oocyte is aspirated.  The fluid is immediately examined by the embryologist and the oocytes are isolated.  The patient is the brought to the recovery room to rest and is discharged a short time after.  Recovery is rapid and there are no incisions.  Many feel pretty well a couple of hours after the retrieval.  We also will obtain a sperm sample at this time or use frozen sperm if the male partner is unavailable.  The oocytes are then inseminated (IVF) or injected (ICSI) by the embryologist depending on the coexistence and severity of male factor.  Fertilization is assessed approximately 18 hours later and patients are contacted and updated as to the status of their embryos.

4.  Embryo Transfer:  Embryo transfer is performed anywhere from 2-6 days after oocyte retrieval.  The couple will be contacted to discuss the day of recommended transfer and is based on the number of oocytes and more specifically good quality embryos.  Most will undergo a day 5 blastocyst transfer.  The couple would come into the office.  The embryo quality would be reviewed and a digital video link from the microscope in our controlled environment would be utilized to show the actual quality on out high definition monitors.  CDC statistics would be reviewed in regards to the number of embryos to transfer as it relates to pregnancy rate and multiple pregnancy rates.  Recommendations and the reasoning would be reviewed.  Embryo transfer would then be performed which is essentially the same as the “mock” as noted above.  We do administer Valium for relaxation/stress reduction purposes just prior to transfer.  

The embryo catheter is advanced to the optimal location under ultrasound guidance and the chosen number of embryos are released.  The patient then lays flat for approximately 30 minutes.  That day should be a relaxing day.  Normal activity may resume subsequent to the day off with the exception of exercise and sexual intercourse.

5.  Additional Techniques:

A.  Intracytoplasmic Injection (ICSI): Utilized for cases of severe male factor or surgically retrieved sperm.  This technique unfortunately is over-utilized in this country and has absolutely no benefit for couples with essentially normal sperm.  This has been highlighted by our society, however, despite recommendations is still promoted and only increases costs without any benefit.  We perform this technique when indicated which is in approximately 30% of our cycles.

B.  Assisted Hatching (AH):  Assisted hatching is a technique performed prior to embryo transfer in which the “shell” or zona of the embryo is opened slightly to improve embryo implantation.  This also has certain indications.  For example, women over 38 years old or with a history of previous failed implantation may benefit.  This can be performed either with a Tyrode’s solution or laser manipulator.  We utilize a state-of-the-art laser system when indicated.

C. Embryo Quality Assessment: Genetics 

Genetic Screening (PGD, PGS, CCCS): Preimplantation Genetic Diagnosis, Preimplantation Genetic Screening, Comprehensive Chromosomal Screening

The most likely cause of a failed IVF cycle relates to embryo quality.  This is dictated partly by the stimulation cycle itself but by far is related to the underlying diagnosis and age of the patient.  Although embryos may be graded as high quality, morphologic (the way they look) assessment is subjective and limited.  Dr.  Lipari has contributed significant knowledge to the fertility community in regards to his publications on embryonic metabolism and its utility for the prediction of embryo quality in a much more objective way.   He currently holds a patent for this particular technology.  Although not currently available, this has improved our knowledge of embryonic progression and the predictability of blastocyst formation.

Objective methods that are currently available include assessment of the chromosomal components of embryos.  Most specialists would agree that by far the majority of embryos are chromosomally abnormal.  The transfer of abnormal embryos would most commonly result in no pregnancy or miscarriage.  This is the likely reason for the reduced pregnancy rates in women, especially over 35 years of age.

Recent technological advances have now enabled the preimplantation embryo to be screened for these chromosomal changes, obviating the transfer of embryos that are not chromosomally competent.  Preimplantation Genetic Diagnosis (PGD) has been around for some time and has been useful for the evaluation of single gene defects in couples that are carriers of a particular genetically inherited condition.  For example, a couple in which each partner has a single CF (cystic fibrosis) mutation has a 25% chance of having a child effected by this difficult condition.  PGD can help identify embryos that are affected so only the normal embryos or carriers may be transferred.  This is used for many other conditions as well.  In the past, our technology was limited to single gene defects or screening only 7-9 chromosomes.  Now we are able to screen all the chromosomes.  

It is possible to screen the preimplantation embryo for chromosomal problems including single gene defects and aneuploidies (changes/abnormalities in chromosomal number and causes of miscarriage).  Some have also desired this technique for gender determination.  A biopsy of 7-9 cells is taken from the day 5 embryo and the chromosomes are evaluated.  Chromosomes and gender are determined prior to embryo transfer.  We believe that this has the ability to significantly influence success rates in a positive way.