Advanced Embryology Services

advanced-embryology-servicesOne of the quality measures of a successful fertility program is the experience and success of its advanced lab services. Our Reproductive Studies Lab has led the region in high-tech advancements since the center’s beginning. This has meant convenient access to the best treatment available for both our local patients and for those who drive several hours to benefit from our proven success.

Our lab has helped the center achieve the following significant advancements, all of which have expanded options for our patients:

  • First in Tristate to achieve pregnancy using blastocyst stage embryos (more mature embryos), helping to significantly reduce incidence of multiple births.
  • First Tristate center to achieve pregnancy using IVF and preimplantation genetic screening and the first to achieve live birth with preimplantation genetic diagnosis.
  • First Ohio live birth using hamster zona (egg shell) to freeze single sperm cells – a breakthrough treatment for men with extremely low sperm counts.
  • First center in Tristate to achieve pregnancy and live birth using frozen eggs, providing more options for cancer patients and women who wish to delay starting a family.
  • First in Greater Cincinnati to achieve pregnancy and live birth with intracytoplasmic sperm injection (ICSI), a male factor infertility breakthrough.

To read more about our center firsts, click here.

In Vitro Fertilization (IVF)

In vitro fertilization (IVF) is the union of the ovum (egg) and the sperm outside the woman's body. The first step in this process is to administer fertility drugs to the woman to ensure the development of multiple eggs for fertilization. We then retrieve her eggs through an ultrasound-guided surgical procedure in our in-office surgical suite under anesthesia. Next, we fertilize the eggs in our lab, and we culture (grow) resulting embryos until they reach the blastocyst stage.

Once embryos reach the blastocyst stage (a more mature stage of embryo growth), we transfer a minimum number – one to two, depending on each patient – to the woman’s uterus using a non-surgical, ultrasound-guided procedure called embryo transfer. Non-transferred embryos may be cryopreserved (frozen) for future use.

Our Center recommends IVF only when all other means of achieving pregnancy have failed. Indicators appropriate for IVF include:

  • Female tubal factor infertility (fallopian tube damage caused by endometriosis, sterilization, surgery or infection)
  • Endometriosis
  • Male-factor infertility and
  • Unexplained infertility

A diagnosis of unexplained infertility requires a very thorough workup that must include a semen analysis, HSG, failed Clomid ovulation induction, failed hMG cycles and ovarian reserve screening that yields normal results.

IVF with ICSI (Intracytoplasmic Sperm Injection)

Since the mid-90s, fertility centers around the world have scrambled to master the technique of intracytoplasmic sperm injection (ICSI), a breakthrough procedure that has revolutionized treatment for male factor infertility and boosted national IVF success rates significantly. Our Center was the first in the Tristate to achieve fertilization with this technique and the first in Greater Cincinnati to achieve pregnancy, just one year after the first international pregnancy was announced.

ICSI's innovation lies in the ability of specialists to inject a single sperm directly into an egg. Until ICSI, low sperm counts and sperm with poor movement or shape posed barriers to fertility since the sperm possessed a significantly reduced potential to fertilize eggs. Today, ICSI, coupled with IVF, offers couples significantly higher chances at fertilization. Live birth rates for couples requiring ICSI are similar to rates for couples not requiring ICSI, assuming the woman is of similar age.

Which couples need IVF with ICSI?

Indications for IVF and ICSI are:

  • severely low sperm count (usually less than 5 million sperm/ml)
  • severely low motility (usually less than 20 percent even with normal sperm counts)
  • normal percent motility but with a poor motility grade (grade is how well the sperm swim)
  • severely abnormal morphology (sperm shape)
  • failed or poor fertilization in a previous IVF attempt

Does the Man's Age Affect the Couple's Chances of a Live Birth?

The man's age is not nearly as important as the woman's age. Even if there are problems with a man's sperm, with ICSI, fertilization can still be achieved independent of the man's age. Men over age 50 do have a small but significant reduction in live birth rates compared to younger men. There's also a slight increase in the incidence of genetic abnormalities in the child (i.e. Down's syndrome) as the man ages, but the increased risk with advancing age is not nearly as high for men as for women.

Fertilization rates using ICSI typically are equal to or greater than 75 percent, with damage to the embryo approaching zero.  

IVF with IMSI (intracytoplasmic morphologically-selected sperm injection)

Intracytoplasmic morphologically-selected sperm injection (IMSI) vastly improves the selection of normally-shaped sperm (normal morphology) for higher pregnancy rates and reduced miscarriage rates and is most appropriate for couples with severe male infertility. Our Center was the first in the Tristate and one of only a few in the country to offer this advanced technology.

The technique is an improvement of ICSI (see above). But instead of magnifying an individual sperm by 400 times to select the best sperm for egg injection, IMSI features a specially-configured, high-powered microscope that achieves magnification of greater than 6000 times. This allows the embryologist to look at sperm in greater detail to detect subtle structural damage/alterations that a normal ICSI procedure microscope cannot detect.

The advanced IMSI technique is significant for couples with severe male infertility and repeated unsuccessful IVF attempts since studies have shown increased genetic abnormalities (DNA fragmentation) in the sperm and embryos of this population.

Patient criteria best suited for IMSI include:

  • Failed fertilization cycle
  • At least 2 failed IVF or ICSI cycles
  • History of miscarriages
  • Male partner of advanced age
  • High DNA fragmentation index
  • High incidence of genetically abnormal embryos   

IVF with Blastocyst Stage Embryo Transfer

Our center has a long history of growing embryos to the blastocyst stage, the preferred industry standard for embryo culturing. In 1997, we were the first in the Tristate to achieve pregnancy using blastocyst stage embryo transfer. We are the only center in the area that routinely transfers embryos at the blastocyst stage, with more than 95 percent of all embryo transfers performed using this technology. This is possible due to our expert Reproductive Studies Lab, which has perfected the culture medium used to grow embryos to the blastocyst stage.

The advantages of blastocyst transfer to patients are higher pregnancy rates and fewer embryos transferred to the uterus per IVF cycle. Transferring fewer embryos to the uterus results in lower rates of twins and high order multiple pregnancies (triplets and above).

Higher Pregnancy Rates via Higher Quality Embryos

Traditionally, embryos are grown for 3 days prior to uterine transfer. A better alternative is to allow embryos to grow for an additional 2 to 3 days to the blastocyst stage. These more mature, multicellular embryos have survived the major metabolic hurdle of the 8-12 cell stage and are capable of performing much more complex and advanced functions to initiate implantation in the uterus. Studies have shown implantation rates of about 20 to 25 percent for day 3 embryos compared to 50 percent with day 5 or 6 blastocysts.

Embryos that grow to this advanced blastocyst cell stage allow our experts to see the quality and number of two cell types that are important for the developing fetus, namely trophectoderm cells and inner cell mass (ICM).

blastocyst

The blastocyst, when magnified, resembles a tennis ball, with a clump of cells (the inner cell mass) located at one of its poles. The inner cell mass is responsible for the actual fetus. The trophectoderm cells are responsible for forming parts of the placenta. These cells are necessary for implantation. If an embryo contains only inner cell mass cells, it cannot implant. If an embryo has only trophectoderm cells, it can implant, but a fetus will not form, and the result will be an early miscarriage. It is impossible to detect these important characteristics with day 3 embryos.

On average, only 30 to 50 percent of embryos will survive to become blastocysts. So reaching this stage is in itself an indicator that these embryos will have the highest potential to initiate pregnancy. Failure of other embryos to reach the blastocyst stage is most likely due to defects in the egg or sperm, including genetic defects. These same embryos also would not survive in the uterus.

Lower Risk of High Order Multiples

The only way a day 3 embryo transfer can approach the success rate of blastocyst transfer is to transfer more embryos, which increases a patient’s risk for a high order multiple pregnancy (triplets and above). Multiple implantation can cause serious complications and health risks to both mother and child. Blastocyst transfer reduces these risks without reducing pregnancy rates by allowing our experts to transfer fewer, yet higher quality, embryos.

Higher Quality Frozen Embryos

In the past, centers froze day 3 embryos without the benefit of knowing which embryos would provide higher implantation rates. Not only do blastocysts reveal this knowledge, but they also freeze and thaw better than day 3 embryos. Our center only freezes embryos at the blastocyst stage to offer our patients the highest possible pregnancy rates.

Frozen Embryo Transfer

Frozen embryo transfer is a procedure using embryos that were not transferred during a fresh  in vitro fertilization (IVF) cycle but were instead frozen, or cryopreserved, for later use.

While we now routinely freeze embryos at the blastocyst stage, previously, embryos were frozen at an earlier stage of development. Our embryologist will thaw and culture such embryos to the blastocyst stage – our quality standard for achieving the highest likelihood of pregnancy. Meanwhile, one of our physicians will meet with the patient to begin preparation of the uterine lining (endometrium), which will be synchronized with the development stage of the thawed embryos. The patient will take minimal Estrogen doses to begin building her uterine lining and progesterone support, to be continued until early pregnancy confirmation.

Hamster Zona/Low Sperm Count Cryopreservation

(Freezing Single Sperm Cells)

Previously, men with exceptionally low sperm counts could only benefit from infertility techniques such as intracytoplasmic sperm injection if sperm could be harvested at exactly the same time as a woman’s egg was being retrieved. This typically involved a surgical procedure known as testicular sperm extraction. Harvested sperm could not be frozen using traditional methods because the low volume of sperm cells are nearly impossible to find in the solution used to protect sperm during freezing.

Today, thanks to breakthrough technology, even one sperm cell can be safely stored for as long as needed in the empty shell of a hamster egg. The process pushes the treatment of male-factor infertility nearly to the point of nonexistence.

The Bethesda Fertility Center was the first in Ohio, and only one of two centers nationally, to achieve success with this technology.

Laser-Assisted Hatching

Laser-assisted hatching is one of several methods available to help an embryo hatch from a fertilized egg’s protective shell and attach to the uterus. The technology is helpful in cases where the shell of a fertilized egg is thicker or harder than normal. Laser-assisted hatching can greatly increase a woman’s chances of becoming pregnant.

Normal Hatching

The unfertilized egg is surrounded by a soft outer shell called zona pellucida. The zona pellucida ensures that only one sperm cell enters and fertilizes an egg. After fertilization, the zona pellucida holds the cells of the embryo together. When an embryo is five or six days old and is at the developmental stage known as blastocyst, it needs to escape, or hatch, out of the zona. Once an embryo has hatched from the zona, it is able to implant into the endometrial lining of the uterus and establish pregnancy.

Barriers to Normal Hatching

Older women have a tendency to produce eggs with a thicker outer shell than younger women’s eggs. The same is true for women with high blood levels of follicle stimulating hormone (FSH). Culture media conditions also may contribute to the hardening of zona pellucida, especially with frozen, thawed embryos.

When an egg has a harder zona pellucida, the embryo may not have enough energy to crack open the shell or time to complete the hatching process and thus, cannot establish pregnancy during its implantation window. In these cases, hatching of the embryo prior to implantation is necessary to achieve pregnancy.

New Technology to Promote Hatching

At the Bethesda Fertility Center, we offer the latest state-of-the-art technology for zona hatching using laser-assisted hatching – a gentle and safe way to weaken part of the zona pellucida. Laser-assisted hatching features the creation of a small hole in the zona of an embryo using laser technology. This allows the embryo to hatch more easily, therefore increasing the chance of implantation.

Laser-assisted hatching is performed just before an embryo transfer procedure. There is no evidence that laser-assisted hatching is harmful to embryos, and recent research shows that women who have undergone repeated IVF treatments without success significantly increase their chances of pregnancy with assisted hatching.

Embryo Cryopreservation

Patients who undergo in vitro fertilization and have more embryos than needed for transfer may choose for those embryos to be cryopreserved (frozen). Embryo cryopreservation offers additional opportunities for pregnancy at a later date without the time and expense of another egg retrieval.

Preimplantation Genetic Diagnosis and Screening

(PGD/PGS with IVF)

Advances in human genetic studies have enabled us to identify several genes that not only are responsible for our physical traits but also for inherited diseases. New technologies are now available to screen embryos at their earliest stages of development, allowing us to select embryos that are free of genetic disease and that contain the normal number of chromosomes. These embryos, when transferred to the uterus, will have the highest rate of implantation and the highest possibility for a successful, normal pregnancy.

Two different procedures are available for patients at risk of having children affected by an inherited disease or abnormal chromosome numbers. Patients wishing to diagnose their embryos for an inherited genetic disease may use a procedure called preimplantation genetic diagnosis (PGD). Patients with a history of recurrent pregnancy loss and/or of advanced age may use a procedure called preimplantation genetic screening (PGS), which evaluates the number of chromosomes.

How Does PGD Work?

PGD is an invaluable technology for patients who are carriers for genetic diseases. The technology can diagnose embryos with no inherited mutated genes to promote a higher likelihood of healthy offspring who are free from genetic disease. Patients who choose to have their embryos diagnosed with PGD must undergo  in vitro fertilization (IVF) with ICSI to produce a sufficient number of embryos for diagnostic testing.

In IVF, the female partner receives fertility medication to stimulate her ovaries to produce multiple eggs. Eggs are then removed from the ovaries and fertilized in the laboratory with the male partner’s sperm. Resulting embryos are then cultured for five days to the blastocyst stage. A small cellular sample is then removed from growing blastocysts on day five and sent to a highly specialized molecular genetics diagnostic laboratory. This process does not harm the embryos, and they continue to grow as they otherwise would in the laboratory while awaiting test results.

Embryos determined to be free of genetic disease may be transferred on day six of embryo growth. Sometimes, due to testing protocol limitations, which can take several hours to days, embryos might be frozen while awaiting test results. In these cases, a frozen embryo transfer will be arranged after all genetic testing results have been received.

When is PGD Recommended?

PGD is indicated for individuals or couples who know they have or carry a specific gene defect and are thus at risk of passing the condition on to their child. There are many ways to determine if a female or male partner carries a genetic abnormality due to his or her previous history of child birth with a genetic birth defect or serious medical condition. Family members may carry gene mutations, or a condition may be found during a routine pretreatment genetic screening.

We routinely test patients for the most common inherited genetic diseases, such as cystic fibrosis. In addition, a patient’s ethnic background may also prompt us to discuss additional genetic testing for such conditions as sickle cell anemia, thalassemia and Tay-Sachs disease. Once a genetic abnormality has been identified, a center nurse will work with you to coordinate your PGD cycle.

Accuracy of PGD testing

The accuracy of PGD is generally 95 to 99 percent. Patients wishing to confirm a PGD diagnosis are advised to undergo additional genetic testing such as amniocentesis and chorionic villus sampling (CVS) during early pregnancy. Additional testing will confirm the preimplantation genetic diagnosis to near 100 percent accuracy.

Disorders for Which PGD is Offered

Any genetic disease whose gene mutation(s) sequence has been characterized can be identified by creating specific markers. To access a comprehensive list of diseases for which PGD is available, click here.

How Does PGS Work?

Preimplantation genetic screening of embryos is highly recommended for patients who have experienced multiple (recurrent) miscarriages or repeated unexplained IVF embryo implantation failures. We also highly recommend PGS for patients of advanced maternal age. With this genetic testing, embryos are biopsied and analyzed for all chromosomes. Too few or too many chromosomes may indicate a number of conditions that could cause implantation failure, early miscarriage or a baby with Down syndrome, a genetic condition marked by significant physical and cognitive difficulties.

PGS also can allow patients to identify the sex of the biopsied embryos. However, our center does not perform PGS for family balancing purposes ( i.e., transferring embryos of a particular sex only and discarding normal embryos of the other sex). We only consider sex-selected embryo transfer if a patient and/or her partner has a lethal sex-chromosome-linked genetic disorder.

Once genetic screening has been discussed and decided upon, a center nurse will work with you to coordinate your PGS cycle.