In Vitro Fertilization (IVF) Process - Crozer-Keystone Health System - PA

In Vitro Fertilization (IVF)

IVF, a form of assisted reproductive technology (ART), is a treatment methods for many couples who suffer from blocked tubes, failed multiple infertility treatments or who are labeled as unexplained infertility.

How Does IVF Work?

In Vitro Fertilization (IVF)IVF involves extracting a woman's eggs, fertilizing the eggs in the laboratory with sperm and then transferring the resulting embryo(s) into the woman's uterus through the cervix (embryo transfer) where it can develop.

Controlled Ovarian Stimulation

The very first step to any of the assisted reproductive technology (ART) processes is to induce the development of multiple follicles in the ovary rather than the single follicle that matures in a monthly natural cycle. Reproductive Endocrinologists agree that the chances for pregnancy are greater if more than one oocyte is fertilized and transferred to the uterus during the IVF cycle. Multiple follicular developments are accomplished by administering supraphysiological doses of the hormones naturally produced during the cycle (follicle-stimulating hormone and luteinizing hormone). Today these hormones (Gonal F, FSH and Luveris, LH) are recombinant, produced in culture and are very pure. Their subcutaneous mode of injection renders the daily administration of FSH and LH more tolerable than the previous generation of fertility medication.

The natural production of these hormones must be suppressed to prevent spontaneous ovulation prior to the oocyte retrieval. This is achieved with Lupron prior to (on day 21 of the previous cycle) or Lupron or Cetrotide at the start of the start of the cycle (cycle day 2). This regimen allows us to control ovarian hyperstimulation and the timing of the follicular aspiration. In addition to suppressing specific pituitary function, Lupron also assists to synchronize the follicles and produce a better quality cohort for retrieval.

Ovarian stimulation is monitored through transvaginal ultrasound and frequent hormone evaluation. Estrogen production by the growing follicles as well as direct measurement by ultrasound guides our interpretation as to when we should trigger final maturation with human chorionic gonadotropin (hCG) or Lupron. The hCG simulates the patient’s natural LH surge responsible for the final pre-ovulatory changes in the oocytes, preparing them for fertilization. Even with pituitary down-regulation, spontaneous ovulation does occur, albeit rarely (3%). Thus, some programs still monitor endogenous luteinizing hormone production or progesterone throughout the stimulation cycle. To stimulate the final maturation of the oocytes in preparation for the retrieval, human chorionic gonadotropin is administered ~ 36 hours prior to the oocyte retrieval.

Oocyte Retrieval

Oocyte retrieval is accomplished by transvaginal-guided aspiration. This minor surgical procedure can be performed in a physician’s office under intravenous sedation, as the patient is asleep for such a brief period. The ultrasound locates the ovarian follicles and the distance from the vaginal ceiling. A

guide attaches the retrieval needle directly to the ultrasound probe. In most instances, the needle is passed through the vaginal wall during the aspiration. The follicular contents are examined in the laboratory and the oocytes separated from the fluid and cellular components. Laparoscopy has been described in the past as an alternate method for oocyte retrieval if the ovary is inaccessible through the vagina or even through the bladder, however this procedure is used very infrequently.

Culture and Fertilization

After the oocytes have been identified, they are rinsed and incubated until it is time for insemination, either by conventional methods or via intracytoplasmic sperm injection. During the time of the retrieval, the male specimen is prepared for insemination in the Andrology Laboratory. Approximately 6-7 hours after the retrieval, the purified, highly motile fraction is added to the oocytes for conventional insemination. At a concentration of ~30,000 motile sperm/ 3 oocytes, the culture dishes are returned to the incubator until fertilization is assessed the following morning. Oocytes are assessed for evidence of fertilization at 15-18 hours post insemination and returned to the incubators until growth is assessed the following day.

Assisted Embryo Hatching (AEH)

The oocyte and preimplantation embryo is surrounded by a gel-like coating, the zona pellucida, which offers protection during fertilization and transport through the reproductive tract. Through the early stages of development, in vivo and in vitro, the zona will thin as the embryo grows and expands. This thinning will eventually result in a breach of the zona whereby the embryo can escape, as the zona’s protective role is unnecessary and actually inhibitory to implantation at this time.

It is thought that in certain classifications of patients, the embryo fails to hatch from the zona pellucida; therefore, implantation is not established. Assisted embryo hatching (AEH) is a laboratory procedure performed prior to embryo transfer. AEH is an attempt to assist in the natural hatching process by creating a small, chemically induced breach in the zona. We routinely perform AEH on women 38 and over, during frozen embryo transfers, after a previous failed attempt, if the zonae fail to thin in culture and if the patient’s baseline follicle stimulating hormone is elevated.

Embryo Transfer

The embryo transfer typically occurs 3 or 5 days after the oocyte retrieval. The procedure is performed in the clinic on an outpatient basis and no anesthesia or analgesia is used. The embryos are transferred to the uterus via a small catheter similar to that used during the mock transfer during your stimulation. The catheter is placed through the cervix into the endometrial cavity under ultrasound guidance. The embryo transfer is a quick procedure with essentially no discomfort. Patients are encouraged to resume normal activity the following day, with a few defined restrictions.

Blastocyst Transfer

As implantation rates increase with advancements in both clinical and laboratory technology, the incidence of multiple gestation also increases. Extending the growth period of the embryos in culture

(from days 2 or 3 to day 5) provided an additional power of selection for embryo transfer, as not all embryos possess the same capacity for growth. Embryos that continue to cleave appropriately during the extended culture period (days 4 and 5) have overcome a major hurdle in early preimplantation development and are considered inherently heartier than the remaining cohort which failed to progress.

We offer blastocyst culture to reduce the number of embryos transferred in any one cycle. Our goal is to reduce the chance of multiple gestations, which puts the pregnancy at a higher risk for loss, premature labor and pregnancy complications. As the blastocyst stage is more developmentally competent and physiologically appropriate for the uterine environment at this point of the cycle, it makes sense that the implantation potential is greater.

We welcome the opportunity to discuss blastocyst transfer should any questions arise.