In order for an embryo to implant in the uterus, it must first emerge (hatch) from its thick outer layer, the zona pellucida.
‘Hatching’ is part of an embryo’s normal development and usually happens without any assistance. In some situations, however, when embryos may not hatch well on their own, we can help facilitate this process using the assisted hatching procedure. The procedure involves making a small hole in the zona pellucida with a laser.
Assisted hatching is recommended for women 41 years or older who are having a transfer on day 3, and for thawed cleaved embryos.
A blastocyst is an embryo with two cell types: the trophectoderm, or outer layer, which may eventually become the placenta, and the inner cell mass that may differentiate into the fetus. Blastocysts usually form by day 5-6 after retrieval.
Patients with many, good quality, cleaved embryos on day 3 benefit from culture of embryos for 2 additional days and transfer of blastocysts on day 5.
The extra 2 days in culture gives additional information about embryo quality, which improves our ability to identify the embryos that are most likely to implant when transferred to the uterus. This results in a higher implantation rate. Because of the higher implantation rate, fewer blastocysts need to be transferred, leading to a lower incidence of multiple births.
However, blastocyst transfer is not a good idea for everyone. If a couple has a low number of embryos, the extended culture may not result in development of any blastocysts. If this were to happen, no transfer would be performed. In these cases it is much better to transfer the embryos to the uterus on day 3.
The cryopreservation procedure provides couples the option of freezing high quality unused embryos for future use. Transfer of thawed embryos is done in cycles with no stimulation drugs or egg retrieval and is less costly.
Only embryos that develop into good quality blastocysts on day 5 or day 6 post-retrieval will be frozen. Approximately 90% of blastocysts survive the freeze/thaw procedure. Pregnancy rates with thawed blastocysts are very similar to that of fresh blastocysts.
The uterine lining is prepared for embryo transfer with estrogen patches and progesterone.
ICSI, intracytoplasmic sperm injection, makes it possible for men with severe male factor infertility to father genetically related children.
Prior to ICSI, many couples with moderate to severe male infertility had little chance of creating a genetically related child and often had to turn to a sperm donor.
ICSI may be performed using ejaculate sperm, sperm retrieved by testicular biopsy, or sperm retrieved by epididymal aspiration.
With the ICSI procedure, a single sperm is injected directly into each mature egg. This greatly increases the probability of fertilization.
ICSI can’t be performed until the accessory cells that surround the egg are removed. This is done with a gentle enzymatic procedure.
Next, the maturity of the egg is determined. ICSI is performed only on eggs that have reached the maturation stage where they have extruded a polar body. Immature eggs are not injected with a sperm because they do not have any chance of fertilizing. If you are having ICSI done, keep in mind that not all the eggs will be mature enough to inject a sperm.
ICSI is done with the egg is held in place by suction. A motile sperm (one that is alive) is chosen to be injected. The sperm is picked up in a very fine pipet. The sperm is brought to the very tip of the pipet before injecting the sperm into the egg so that as little extra fluid as possible is injected into the egg. The pipet with the sperm punctures the egg membrane.
Once the pipet is inside the egg, a small amount of the egg’s content (the cytoplasm) is drawn up into the pipet along with the sperm and the sperm is expelled into the egg. This brings the sperm into close contact with the cytoplasm so that there is a good chance of fertilization.The pipet is then with withdrawn from the egg.
ICSI will cause fertilization in about 75% of oocytes. However, fertilization varies a great deal between couples.
ICSI appears to pose no significant side effects in children conceived using the ICSI procedure. Early concerns about possible genetic abnormalities have not been substantiated. However, sometimes the egg may be damaged during ICSI, or fertilization may not be successful.
Some researchers and clinicians have expressed concern that physically selecting and inserting sperm using ICSI might lead to male offspring with reduced fertility. In nature, the “strongest” sperm usually reaches the egg first and initiates fertilization, whereas in ICSI, a human selects the sperm cell. This impedes the natural selection process. Males born using ICSI are now reaching reproductive age and any reduction in fertility will be documented in the near future. Most clinicians believe these males will not have reduced fertility.
IUI, or intrauterine insemination, is one of the most commonly performed reproductive procedures in the world. IUI has been used in one form or another for almost 200 years.
IUI involves inserting washed, concentrated sperm directly through the cervix into the uterus. “Unwashed” sperm must never be placed in the uterus, as serious and sometimes even fatal allergic reactions can occur.
IUI is useful when there are infertility issues related to a cervix that is scarred and closed, when there are low numbers of sperm, or even if the cause of infertility is unknown.
Cervical mucus must be of the correct consistency for the sperm to swim to the site of fertilization. Active infection of the cervix may impair sperm motility, so should be treated. If cervical mucus is absent or the cervix is scarred due to past cervical surgery, sperm may be unable to pass through the cervix normally.
IUI is sometimes a first-line treatment for unexplained infertility. IUI is often performed in stimulated cycles, meaning Clomid or FSH is given to stimulate follicular development, thus increasing the chances of a successful IUI. When women undergo ovulation induction with FSH, they must come to our office for repeat ultrasound monitoring and estradiol measurements. These tests ensure that the follicles are properly developing and lower the chances of adverse drug reactions such as ovarian hyperstimulation syndrome.
IUI is ideally performed by a trained infertility specialist/reproductive endocrinologist. Infertility specialists undergo years of advanced training in FSH administration and the management of difficult IUI cycles. They have access to laboratories that process sperm optimally, and can also do swim up procedures of semen to improve the IUI specimen.
One IUI risk is that it increases the chance of multiple births because the number of eggs ovulated can be difficult to control. This is unlike IVF, where a set number of embryos are transferred to the uterus. Most of the high order (>4) births reported in the media are the result of IUI cycles that were administered by a non-specialist in combination with injectable FSH. Specialists are trained to limit the chances of this unwanted potential side effect of IUI.
Three IUI cycles will usually be tried, depending upon the couple's history, after which IVF may be the next choice. In some cases of infertility due to issues such as tubal disease, advanced female age, and male factor, IVF is the first-line treatment and IUI is not attempted.
If a woman is ovulating irregularly or not at all, Clomid or Femara may be a first-line treatment to induce ovulation.
If first line medications fail, the next infertility treatment option depends on several patient-specific factors. For some, the next step is stimulated intrauterine insemination (IUI). “Stimulated IUI” means that a fertility drug is used to stimulate the ovaries. In many cases, three cycles of IUI will be tried before moving to more advanced infertility treatments, such as IVF.
IVF is required in a relatively low percentage of patients.Some conditions, such as hyperprolactenemia, respond to infertility treatment using specific medications. In these cases, Parlodel is given to normalize prolactin levels, allowing ovulation to resume.
Sometimes, polycystic ovarian syndrome (PCOS) will respond to infertility treatment with the drug metformin. Metformin sensitizes the cells to insulin; resulting in a lowering of androgen levels (male hormones) and the return of ovulation, often while helping the patient lose weight. PCOS patients often need additional medications, such as FSH.
The surgical treatment of fibroids can sometimes be accomplished through hysteroscopy. Small fibroids, less than about 3 cm, that protrude into the uterine cavity so that they can be seen hysteroscopically, can often be completely removed this way. Removal of such fibroids often makes the menstrual period lighter or improves fertility.
Removing fibroids this way takes a lot of practice, and should be performed only by gynecologists that are specially trained or by reproductive endocrinologists who do this type of surgery frequently.
Fibroids that have any contact with the outside surface of the uterus (the serosa), and fibroids that are large or numerous, have to be removed from the outside of the uterus. Some fibroids may be able to removed with a laparoscope, while others require an open approach to surgery.
When these types of fibroids are large or multiple and causing infertility, they are best removed by a gynecologist or reproductive endocrinologist with such experience. This procedure is termed abdominal myomectomy and is done when preservation of the uterus is desired.
Polyps are focal over-growths of the uterine lining, and are composed of endometrium. Though they can look like fibroids on ultrasound, and cause the same symptoms of infertility or heavy menses, they are typically easy to remove with a hysteroscope.
Tubal Reversal Surgery
Tubal surgery is sometimes performed to reverse a previous tubal ligation (tied tubes). Tubal reanastomosis (surgically “reconnecting” the tubes”) is a reversal of tubal sterilization performed using either microsurgical tubal surgery techniques (laparoscopy) or laparotomy. Dr. Halina Wyczyk and Dr. Cynthia Sites, at Baystate Reproductive Medicine, are the only reproductive surgeons in western Massachusetts offering microsurgical tubal reversal.
In Massachusetts, health insurance will not cover tubal reversal surgery, which presently costs approximately $10,000.
Tubal surgery to reconnect the tubes is more complex than tubal ligation as it involves the use of very thin micro sutures to carefully reconnect the tubes. This type of tubal surgery requires the use of an operating microscope, or another magnifying source, to visualize the fallopian tubes, so it may take from two to three hours to perform.
The success of tubal reversal surgery is dependent upon several factors. One is the amount of fallopian tube remaining after the sterilization. If at least 4 centimeters of healthy tube is present after Fallopian tubes are put back together, then pregnancy is more likely to occur.
If the tubal ligation surgery involved the use of cautery or burning of the fallopian tube, then the pregnancy rates after tubal reversal surgery may be lower. Many patients are more likely to achieve pregnancy by undergoing In Vitro Fertilization (IVF).
Patients who are older than 38 may be encouraged to undergo IVF rather than tubal surgery. Additional tests such as a hysterosalpingogram to evaluate the uterine cavity, hormonal tests, and sperm evaluation will also be needed.
Age is a significant factor for successful tubal reversal surgery. Younger women can attempt multiple natural intercourse cycles after tubal reversal surgery whereas older women may be limited by declining egg quality.
Tubal surgery may present a higher risk of ectopic pregnancy (i.e. tubal pregnancy) compared to IVF. An early pregnancy test and ultrasound evaluation can help make the diagnosis. Frequently, early therapy (with either surgery or medication) can save the involved fallopian tube.
Sperm freezing can be done for several reasons:
- Couples undergoing infertility treatment who choose to have backup samples in storage.
- If the male is going through cancer treatment or a medical procedure which can lead to male infertility.
We are not a donor sperm bank. Baystate's Reproductive Biology Lab will store donor sperm that is ordered from a donor sperm bank. and will thaw and analyze specimens at the time they are used.
When there are no sperm in the ejaculate, they can often be withdrawn directly from the male reproductive tract using testicular sperm extraction (TESE) or micro epididymal sperm aspiration (MESA).
Most cases of male infertility do not respond to fertility medications and none of the “sperm enhancers” have been proven to significantly increase sperm quality or quantity.
One exception is the infertile male who has extremely low levels of FSH and LH, a rare condition known as hypogonadotropic hypogonadism. These patients often do well with FSH injections, and sometimes clomiphene, but the treatment period is long and very expensive.