Induction of Ovulation
From birth, all the eggs a woman will have for life are stored in her ovaries. After she goes through puberty, one of these eggs will mature every month. The ovary releases the egg (an event called ovulation), and the egg then travels down the Fallopian tube, available for a sperm cell to fertilize it. When the egg does not get released every month (called anovulation) or ovulation is weak (called ovulatory dysfunction), infertility may result.
Anovulation and ovulatory dysfunction are common reasons for infertility
Typically, anovulation or ovulatory dysfunction is accompanied by menstrual cycle irregularities. If anovulatory cycles are longer than 32-35 days or shorter than 24 days it can result in infertility. Anovulation or ovulatory dysfunction can be corrected and treated by induction of ovulation with several different medications.
Treatment of anovulation or ovulatory dysfunction
There are a number of oral medications we use which enhance ovulation—clomiphene citrate (Clomid) and letrozole are the two most common. These medications can by augmented by Ovidrel or hCG, human chorionic gonadotropin.
Once effective ovulation is induced, other fertility enhancing methods may be used as well. This infertility treatment is often combined with intrauterine insemination or IUI.
If oral medications fail to achieve a pregnancy, we may recommend inducing ovulation with injectable medications like Gonal-F, Follistim, Bravelle, Menopur or Repronex which vary in their ease of use and cost. Injectable medication can be used either with IUI to induce ovulation and help achieve a pregnancy, or with in vitro fertilization (IVF).
Careful management of ovulation inducing medications is important
All of the above medications can help induce ovulation in women who are not ovulating at all, and can strengthen ovulation in women who have a weak or dysfunctional ovulation. At the same time, the use of these medications requires careful monitoring.
We want to make sure that a strong ovulation is occurring, yet we want to prevent the ovulation of too many eggs which would carry a risk of multiple pregnancy and ovarian hyperstimulation or OHSS.
We monitor through blood tests, which measure hormone levels, and with pelvic ultrasound examinations of the ovaries, which measures the growing eggs or follicles.
The right dosage of your medications will be individualized specifically for you based on these monitoring results. With appropriate monitoring, these medications are effective and safe, and have helped countless couples achieve successful induction of ovulation and pregnancies.
Intrauterine Insemination (IUI)
Intrauterine insemination (IUI) is sometimes also referred to as artificial insemination. It is the most basic of the assisted reproductive technologies (ARTs). Because it is the simplest technique which we can use to enhance your fertility, we often recommend it as an initial form of treatment for mild fertility problems. We often use it in combination with ovulation induction.
IUI involves placing sperm directly into the woman’s uterus, close to the openings of the Fallopian tubes.
Performing an intrauterine insemination improves the chances of a successful pregnancy, compared to natural intercourse. During intercourse, the sperm is deposited into the vagina and must swim all the way through the cervix (the entrance to the uterus), through the uterus, and then through the Fallopian tubes where the sperm cells wait for the egg. The journey is so difficult for the sperm that only one out of every million sperm successfully survives and is able to meet the egg in the fallopian tube.
IUI improves these chances for several reasons:
- The sperm are prepared in the laboratory for the IUI procedure by swim-up, gradient centrifugation, or other sophisticated techniques which concentrate the sperm in a nutrient-rich media. This enhances their motility and overall quality.
- We place the concentrated sperm high up inside a woman’s uterus during an IUI, so most of the journey to the egg is eliminated. The proximity to the egg, timing, and superb vitality of these sperm maximizes their chances of surviving the journey to the egg and achieving fertilization.
- A woman’s cervix, the entrance into her uterus, produces mucus which can sometimes be hostile to sperm and prevent the sperm cells from swimming through the cervix. This problem, sometimes called dysmucorrhea or cervical factor, can result in the cervix acting as a barrier to the sperm. IUI bypasses this problem because the sperm are placed beyond the cervix.
Use with Induction of Ovulation
We use insemination in combination with hormonal medications to induce or enhance a woman's ovulation. We have found that IUI is a useful treatment for women with ovulation disorders, cervical factor, partners of men with low sperm counts, and couples with unexplained infertility.
About the IUI Procedure
The physicians at the Fertility Institute perform the IUI using sperm produced by an intimate partner. We also offer IUI using rigorously-screened donor sperm for same-gender couples, single women, and couples with no sperm at all.
The IUI process itself is painless, and does not involve any needles or sharp instruments. It only takes about five minutes and is performed in an examination room, where a spouse or partner can participate in the process.
At the appropriate time of the cycle, the prepared semen sample is loaded into a long, thin, flexible tube (catheter). The catheter is gently threaded through the natural opening of the woman’s cervix and guided to the top of her uterus, where the sperm are gently placed.
Following the IUI procedure, usual daily activities can be resumed. There is no need to take the day off from work or go on bedrest.
In Vitro Fertilization
Medical science and IVF technology have advanced enormously since the late 1970’s when the first IVF pregnancies were achieved. The success rates of IVF treatment can now be as high as 80% in the best prognosis patients.
In vitro fertilization (IVF) is the most advanced procedure available today to help couples with infertility to achieve a pregnancy. The physicians of the Fertility Institute of NJ and NY are extremely proficient and experienced in each aspect of IVF. IVF is the most effective treatment for women and couples who suffer from infertility related to blocked Fallopian tubes, endometriosis, pelvic scarring from previous surgery or infections, or low sperm counts.
In vitro fertilization is also very successful for women and couples who have unexplained infertility and who have not successfully conceived with milder forms of treatment such as ovulation induction and intrauterine insemination (IUI).
The IVF process can be divided into 4 parts:
IVF Stage 1: Ovarian Stimulation
The first phase of IVF is controlled ovarian hyperstimulation or COH. We use various combinations of injectable hormones including Gonal-F, Follistim, Bravelle, Menopur and Repronex to stimulate a woman’s ovaries into preparing more than one egg.
Every egg develops within a sac of fluid called a follicle, and hormonal stimulation of the ovaries results in the development of several follicles. We perform this stimulation under careful monitoring, using blood tests to measure hormone levels and pelvic ultrasound examinations of the ovaries to assess the maturation of the growing follicles. We adjust the dosage of medications as necessary based on this monitoring.
This type of ovulation induction is more assertive than for IUI, because having multiple eggs available during an IVF cycle is associated with better chances of pregnancy.
IVF Stage 2: The egg retrieval phase
When the ovarian follicles are large, indicating that the eggs are mature, we give the woman a triggering injection of human chorionic gonadotropin (hCG). This triggers the final maturation of the eggs.
Approximately 36 hours after the hCG injection, we retrieve the eggs under ultrasound guidance. This technique helps us to identify the follicles containing the eggs and to avoid any injury to surrounding structures. We insert a thin needle through the wall of the vagina and guide it into the follicles. The mature egg is then gently removed.
Egg retrieval is done here at the Institute’s surgical suite, usually under conscious sedation or light anesthesia. This procedure takes approximately 15 minutes.
IVF Stage 3: Fertilization and embryo culture
In vitro culture of the early embryos is performed under continuous carefully-controlled conditions in the embryology laboratory of the Fertility Institute of NJ & NY. As soon as each egg is removed during the egg retrieval, it is placed in a special culture medium in the lab. Several hours later, the eggs are inseminated with the sperm.
In vitro embryo development is carefully monitored by our embryology team. Successful fertilization of the eggs can be seen under a high-powered microscope on the day following egg retrieval.
IVF Stage 4: Embryo transfer
After the early embryos have developed in vitro for several days within the laboratory, they are ready to be placed into the woman’s uterus in a procedure called the embryo transfer. The embryo transfer itself is painless and does not involve any needles or sharp instruments.
The embryo or embryos are loaded into a long, thin, soft tube (catheter). Under the guidance of ultrasound, the catheter is threaded through the natural opening of the woman’s cervix and guided to a spot near the top of her uterus. The embryos are gently placed through the soft tip of the catheter.
The embryo transfer procedure is performed here at the Institute in our embryology suite and takes approximately ten minutes.
We will perform a pregnancy test 7-10 days after the embryo transfer. We know that this waiting time is difficult for most of our fertility patients and we support you full-heartedly during this period. By the 7th-10th day after the embryo transfer, we can confirm that a pregnancy has started to develop. Early pregnancy development is supported and monitored in the following several weeks by the Institute’s physicians with blood testing and ultrasound examinations.
Traditionally IVF has involved transferring embryos on the third day of development, when they contain 6-8 cells. However, there are several important changes that happen to the embryo between the third and the fifth day of development.
In a day-3 embryo, none of the cells have differentiated yet, which means that each of the eight cells is fully capable of forming any human tissue or cell. By the fifth day at the blastocyst stage, however, differentiation has begun, and the cells within the blastocyst form different groups. The inner group of cells called the “inner cell mass” is destined to form the actual body of the fetus. The outer ring of cells is destined to form the placenta.
Extending culture until the 5th day of development of the embryo, when it reaches the “blastocyst” stage and contains hundreds of cells, may be advantageous for many patients.
The Advantages of Blastocyst Transfer
In a natural pregnancy the embryo arrives in the uterus at the blastocyst stage. It is at this blastocyst stage that implantation, or attachment to the lining of the uterus, occurs.
The stronger, hardier embryos are more likely to survive to the blastocyst stage than the weaker embryos. Extending culture of the embryos until day 5 helps us facilitate this natural selection process and allows us to transfer the best quality embryos with the highest pregnancy potential into the uterus.
In addition, performing a blastocyst transfer can reduce the risk of multiple pregnancy, since only a few highly selected embryos are transferred in an IVF cycle.
Although embryos’ nutritional and culture requirements become much more complex as they develop from day 3 to day 5 embryos, the Institute’s state-of-the-art laboratory and experienced embryology team regularly performs extended culture and blastocyst transfer with great reliability and success.
While IVF is the most advanced fertility technology, micromanipulation is a parallel assistive technique that improves success rates for achieving pregnancy and helps eliminate unhealthy embryos. There are several ways in which eggs, sperm, and embryos can be micro manipulated under a high-power microscope to facilitate fertilization and enhance implantation and successful pregnancy.These techniques, collectively referred to as micromanipulation, involve manipulating the eggs, sperm, and embryos under a high-power microscope. Special microscopic glass instruments are then used to achieve the desired outcome.
Micromanipulation requires a high degree of skill and dexterity. Fertility Institute of NJ and NY has a highly trained and extensively experienced embryology team and offers all of the highest-level techniques of embryo micromanipulation. We individualize this benefit to meet our patients' needs.
Intracytoplasmic sperm injection or ICSI
ICSI is a laboratory technique that allows us to inject a single sperm directly into each egg. Fertilization requires the merging of the genetic material of an egg and a sperm. ICSI increases the chances that this will occur by placing the sperm directly into the egg rather than relying on the sperm to drill its way inside on its own as would naturally need to occur.
To prepare for ICSI, all sperm are carefully assessed under the microscope. Our technician draws a single, normal, vigorous sperm into a microscopic glass needle. Under high magnification, the egg is held stationary, and the glass needle is carefully inserted into the jellylike substance of the egg, called the cytoplasm. A single sperm is injected, and the glass needle is withdrawn. The egg, now with sperm within, is kept in culture until the following day, when fertilization can be confirmed.
While ICSI has many uses, it is particularly helpful for men who produce few or slowly motile sperm. Historically, men with gravely low sperm counts were rarely able to father a biologic child. However, with the use of ICSI, such men can and do father healthy children. A normal ejaculate may contain a hundred million sperm, and an ejaculate containing, for example, less than one million sperm is considered to be gravely low and is very unlikely to result in a natural pregnancy without ICSI.
With ICSI, however, a very low sperm count can still lead to perfect success. A woman may produce 10-15 eggs in an IVF cycle, and only a single sperm is needed for each of those eggs if ICSI is used. Thus, as few as 10-15 sperm in the ejaculate may be sufficient to produce a pregnancy.
In fact, even if a man has no sperm at all in his ejaculate, sperm can be aspirated directly from the epididymis or testes (procedures referred to as MESA and TESE, respectively), and ICSI can be used to help these sperm form healthy embryos and successful pregnancies.
Every early embryo is surrounded by a firm, rubbery shell called the zona pellucida. Whether in a natural pregnancy or through IVF, an embryo needs to literally hatch out of this shell in order to implant in the lining of the uterus and develop into a pregnancy. Some embryos have a particularly thick or hard zona pellucida, which may decrease the chances of implantation by making it more difficult for the embryo to hatch out of its shell.
At the Institute, the zona pellucida of every embryo is examined under a high-power microscope. If the zona pellucida appears too thick or tough, we assist hatching with a weak acid solution (called acid Tyrode’s) that gently dissolves parts of the outer layer of the zona pellucida, thus weakening the shell and allowing the embryo to hatch more easily.
With the use of microscopic instruments, the assisted hatching procedure is done safely, with no risk of damage to the embryo. It can increase the chance of a successful implantation and pregnancy. Zona hardening may be related to medications used in IVF as well as increasing age. For these reasons, assisted hatching is performed routinely in women older than 35.
Early embryos can develop fragmentation, which refers to bits of cytoplasm which seem to be breaking apart within the embryo. Fragmentation may be a sign of embryo deterioration, and the fragments themselves may be harmful to the embryo. Defragmentation is performed by the Institute's embryologists to improve embryo quality and increase the chances of a pregnancy.
Preimplantation Genetic Screening (PGS) and Preimplantation Genetic Diagnosis (PGD)
PGS or PGD is a technique whereby we perform genetic testing on embryos in the laboratory, prior to implantation, as a way of ensuring a normal, healthy pregnancy.
The Fertility Institute of NJ & NY offers both of these sophisticated assisted reproductive technologies.
PGS (the "S" stands for "Screening") is used to screen embryos for chromosomal abnormalities.
PGD (the “D” stands for "Diagnosis") can be useful for couples when both are carriers for a genetic disease, for example, and are therefore at risk of transmitting this disease to their future children.
Being able to do PGS or PGD circumvents a couple's need to make difficult medical and moral decisions regarding terminating a pregnancy, in case a genetic abnormality was found after a pregnancy is already advancing.
PGS or PGD can also screen for chromosomal abnormalities such as a translocation or aneuploidy. This can be helpful for older women, women with recurrent miscarriages, and women with repeated IVF cycles that have not yet led to a successful pregnancy.
PGD requires a biopsy of each embryo. In the biopsy procedure, one cell from each three day old embryo is removed for genetic testing. PGD or PGS is performed on day three because at the 8-cell stage of embryo development, none of the cells in the embryo have differentiated yet. This means that any one of the eight cells is fully capable of forming any human tissue or cell. Consequently, removal of a single cell will not damage the embryo or cause any birth defects or missing organs.
Under a high-power microscope and with the use of sophisticated, hydraulically-operated, ultrafine microscopic glass instruments, the Institute’s experienced embryology team stabilizes the embryo, drills a small hole in the zona pellucida, microsurgically removes one of the embryo’s cells, and obtains genetic testing on the cell to provide diagnostic information about the embryo.
The goal of IVF, or any assisted reproductive technology, is to help establish a healthy pregnancy leading to the birth of a healthy baby. While striving to achieve this goal, we try to minimize any associated risks, such as the risk of multiple pregnancy here at the Fertility Institute of NJ & NY.
For a woman undergoing IVF with several viable healthy embryos, we may only transfer a small number, perhaps one or two high-quality embryos into her uterus to maximize the chances of a pregnancy and yet to minimize the risk of a multiple pregnancy.
Preserving Extra Embryos
The remaining embryos are often viable, and have the potential to produce a healthy pregnancy. These embryos can be frozen, or cryopreserved at the Fertility Institute’s cryobank for possible future use.
During the cryopreservation process, embryos are deep frozen in liquid nitrogen, which places them in suspended animation for an indefinite period of time. At some point in the future, either if the initial IVF cycle does not work, or if a child is successfully born from the IVF process and the woman or couple wishes to have another child, cryopreserved embryos can be thawed, and transferred into the woman’s uterus without the need to undergo any additional IVF cycles.
Countless successful pregnancies have resulted through the use of cryopreserved embryos.
Embryos can be cryopreserved using either a slow-cooling method, or a vitrification method which flash-freezes the embryos. Both methods are effective and safe, and the Institute performs both methods as appropriate.
Frozen embryos at the Institute are stored in airtight cryogenic storage tanks which maintain the cryopreserved embryos at several hundred degrees below zero.
While women older than 42 years rarely have extra embryos which are viable and can be cryopreserved, results for younger couples using cryopreservation are similar to the success rates for fresh in vitro fertilized embryos. It is not rare for a single IVF cycle to produce enough fresh and cryopreserved embryos to create 2 or 3 more siblings who are basically “twins” or “triplets” born a year or two apart.
Planning for the Future
Cryopreservation is also used for fertility preservation with much success. This can be especially important to a couple when either partner has been diagnosed with cancer. Chemotherapy treatments can often lead to damage to the ovaries or the testes. Cryopreservation of embryos is one way to preserve the ability to have children in the future.
Many woman face the disappointment of no longer producing eggs or the eggs are no longer viable and cannot be successfully fertilized and result in a pregnancy. Use of donor eggs is an encouraging highly successful alternative for these women.
The egg donation procedure has helped countless couples worldwide to experience a pregnancy and to have children. Dr. Levine, the founding partner of the Fertility Institute of NJ & NY established the first egg donation program in the world, and delivered two of the first 3 babies from egg donation worldwide. All the physicians at the Fertility Institute are well-versed in managing all aspects of egg donation cycles.
The decision to go with egg donation for most couples is a difficult one, but no person or couple who needs it, and chooses to go this route, regrets doing so. The technology of egg donation has brought much happiness and fulfillment to women and couples for whom the hopes of a pregnancy were otherwise dim.
Egg donation involves the following general steps:
Selecting of an egg donor
Many women prefer to use an anonymous egg donor, whose identity they do not know and who will never know their identity. Some women prefer to use a directed egg donor – someone they know and who is willing to donate eggs, such as a close friend or family member.
In either case, during egg donation, the potential egg donor is rigorously screened in a process involving a personal and family medical history, a detailed psychological assessment, testing for infectious and genetic diseases, and of course a full fertility evaluation. A woman or couple considering the use of a particular anonymous egg donor has access, in an anonymous fashion, to relevant details about the potential donor including her age, physical characteristics, ethnic and religious background, family history, and educational and occupational/professional background.
Synchronization of intended mother and egg donor for egg donation cycle
Once the egg donor is selected, the uterus of the intended mother, or recipient, must be synchronized by the Institute’s physicians with the donor’s ovaries and eggs to ensure that the mother’s uterus will be ready to receive embryos when those embryos are ready for implantation. To accomplish successful egg donation, the mother generally needs to take natural hormones such as estrogen and progesterone for several weeks to prepare the lining of her uterus, while the egg donor takes ovarian stimulation medications to help her produce multiple follicles and eggs.
Egg retrieval and embryo transfer
When the egg donor’s follicles and eggs are ready, she undergoes an egg retrieval procedure here at the Institute to remove the eggs from her ovaries. At that point, the egg donor’s role in the process is over.
The donated eggs are fertilized with sperm from the mother’s partner. In the case of a man with no sperm, a single woman, or a same-gender female couple, donor sperm may be used.
The embryos are cultured in vitro in the laboratory, and 3-5 days later embryos are transferred into the mother’s prepared uterus. Pregnancy testing takes place about 7-10 days after the embryo transfer to confirm that a pregnancy has begun to develop. Early pregnancy development is monitored by blood tests and ultrasound examinations during the following several weeks by the Institute's physicians.
BE AN EGG DONOR
Thank you for your interest in our Donor Egg Program. Currently, we are looking for healthy young women between the ages of 21 and 32 to donate eggs to infertile couples.
Potential candidates will undergo a free comprehensive medical and gynecological evaluation, screening for sexually transmitted diseases, and a psychological evaluation. Those volunteers who complete a donation cycle will receive $8,000 for their time and effort. Anonymity and confidentiality are guaranteed.
We hope you will join our group of donors who are uniquely empathetic people, who gain a personal satisfaction from their contribution, and often return more than once to donate.