AMERICAN SOCIETY FOR REPRODUCTIVE MEDICINE – THE GUIDE FOR PATIENTS, 2012
Infertility is defined as the inability to become pregnant after one year of unprotected sex. Women trying to get pregnant for more than a year should seek help from a specialist. However, for women over 35 years of age, the evaluation should start after 6 months of trying so that possible treatment is not delayed. Women who are aware of a factor preventing pregnancy should seek help sooner.
When looking for help, it is known that fertility treatments today offer more hope than ever before. Most patients who seek help in human reproduction fulfill their dream: having a baby.
The gynecologist or urologist can perform the initial investigation or refer the patient directly to a human reproduction clinic. The reproductive specialist will review the medical history in an attempt to identify possible causes for difficulty in getting pregnant. At an initial consultation, the doctor will question the woman about the frequency and regularity of menstrual periods, pelvic pain, abnormal vaginal bleeding, history of pelvic infection, previous illnesses, previous pregnancy, abortion, surgeries, methods of contraception and drug use, and medications. The man will be questioned about the occurrence of genital trauma, surgeries, infections, history of other children, previous illnesses and use of drugs and medications. Each patient will undergo several tests. This can often take time and energy, but the results are very important. When ordering these tests, the doctor will evaluate the tests and medical procedures that have been done previously. So less time and money will be spent.
During the first visit, the emotional stress of infertility should be discussed, a subject that is difficult to share with family and friends. Experts know that the procedures and intimate issues involved in this treatment can be difficult. The patient should always feel free to discuss their problems and frustrations with the specialist and should ask questions whenever they have any doubts.
To understand assisted reproduction tests and procedures, it is important to understand how pregnancy happens naturally. First, the ovary releases an egg that must be captured by the fallopian tube. Sperm ejaculated in the vagina must swim through the uterus to the fallopian tube in order to fertilize the egg. Fertilization usually takes place in the fallopian tube. Subsequently, the embryo (fertilized egg) travels down the tube to the uterus, where it implants and develops. A problem that occurs at any of these stages may not lead to pregnancy.
FACTORS THAT CAUSE INFERTILITY
Ovulation problems are common causes of infertility, accounting for 25% of infertility cases. Ovulation involves the release of a mature egg from one of the ovaries. After ovulation, the ovary produces the hormone progesterone which prepares the uterus for embryo implantation. In cases of normal menstrual cycles, ovulation should take place. Cycles lasting 24 to 34 days (from the start of one menstrual period to the next) are usually ovulatory.
The doctor orders a transvaginal ultrasound to follow up on ovulation. This test assesses the formation of follicles, which are fluid-filled pockets located under the surface of the ovary that contain the immature eggs.
If ovulation is not occurring, the infertile can request tests to investigate the reason and prescribe medications to induce ovulation.
Some patients, even young ones, have poor oocyte quality or even ovarian failure. Research is being done to identify causes and propose treatments. In some cases, making use of an egg bank or shared egg donation program are still the only alternatives.
Permeable and functional tubes are necessary for pregnancy to occur, and there are tests to determine these characteristics. Tubal factors, as well as factors that affect the peritoneum, are responsible for 35% of infertility problems. Hysterosalpingography (HSG) may be performed to assess the fallopian tubes and uterus. Although some tubal problems are corrected by surgery, patients with severely damaged tubes will have a better chance with treatments such as In Vitro Fertilization (IVF). Because of the fact that heavily damaged tubes fill with fluid (hydrosalpinx) and lead to low pregnancy rates in IVF, removal of the tubes before IVF may be recommended.
In approximately 40% of cases, the male factor is the only factor in or contributing to the cause of infertility. Thus, seminal analysis (sperm analysis) is an essential step in male assessment. Other hormonal and genetic tests may be needed, depending on the type and severity of abnormalities found in the preliminary tests.
If seminal anomalies are observed, treatments such as antibiotic therapy for infections, surgical correction of varicocele (dilation of veins in the scrotal sac) or obstruction may be necessary; or drugs that stimulate sperm production. In some men, it may be necessary to obtain sperm directly from the testicles through surgery.
In some cases, the cause of poor sperm quality is not found. Intrauterine insemination (IUI) or IVF may be recommended to correct this failure. If sperm are not found in the seminal analysis or in the surgical procedure (epididymal aspiration or testis biopsy), we can use sperm donors through the semen banks.
Delaying pregnancy is a common choice for women today. The number of women between 30 and 40 years old who want to become pregnant has increased in recent years. A patient who chooses to delay motherhood may not be aware that female fertility declines significantly after age 30.
Fertility decreases with age because few eggs remain in the ovaries and even the quality of eggs that remain is worse than when you were younger. There are hormonal tests that determine ovarian reserve, a term that means age-related fertility potential. Another commonly requested method of assessing ovarian reserve is the use of transvaginal ultrasound to determine antral follicle count (AFC).
Older women tend to have a lower response to ovulation-inducing medications and a higher miscarriage rate than younger women. The chance of forming a chromosomally abnormal embryo also increases with age. Due to the marked effect of age on fertility and pregnancy, it is common for older women to start fertility treatment faster and, in some cases, to undergo more complex procedures. In unsuccessful treatments, there is the option to “adopt” eggs. The ovodonation process is associated with a higher pregnancy rate, regardless of the recipient patient's age. Currently, there is still the possibility of donating embryos.
Cervical pathologies can influence fertility, but they are rarely the only cause. It is important to inform the doctor about the results of biopsies, surgeries, freezing, laser treatments or abnormal preventives. Neck problems are usually treated with antibiotics, hormones, IUI or IVF.
Uterine problems can interfere with embryo implantation or increase the incidence of miscarriages. Hysteroscopy examination may reveal defects in the uterine cavity such as polyps, scars, fibrosis, or an abnormally shaped uterine cavity, which must be corrected before reproductive treatment.
Peritoneal factor refers to abnormalities involving the peritoneum, such as adhesions and endometriosis. Endometriosis is a condition in which tissue that normally covers the uterus begins to grow outside the uterus. This tissue can lodge in any structure in the pelvis, including the ovaries, and is found in 35% of infertile women who have no other identified cause of infertility. Endometriosis is most commonly found in women who experience infertility, pelvic pain, and pain during intercourse. This pathology can affect ovary function, ovarian reserve, fallopian tube function and embryo implantation.
Laparoscopy is a surgical procedure performed to diagnose and treat adhesions and endometriosis.
INFERTILITY WITH NO APPARENT CAUSE
In approximately 10% of cases, all tests performed are normal and there is no defined cause for infertility. In another much larger portion of cases, only a small change is found, but not severe enough to cause infertility. In these cases, infertility is called NO APPARENT CAUSE. Cases identified in this way may have poor oocyte quality, abnormal fertilization of eggs, genetic alterations, compromised tubal function or sperm abnormalities that are difficult to diagnose and/or treat. In these cases, a careful investigation of the lifestyle habits must be carried out regarding the use of medications, tobacco, alcohol, drugs, food, profession that can somehow interfere with fertility.
Medications and IUI have been indicated for couples with infertility without apparent cause with some success. If pregnancy is not achieved, IVF treatment is recommended, which proves to be more effective.
Some men and women carry genetic abnormalities that make them less able to bear children and more prone to miscarriage. One example is translocation, a rearrangement of genetic material. These “defects” can often be identified by genetic testing. Some patients may have a familial disease and want to prevent it from being passed on to their descendants. In more specific cases, an assisted reproduction treatment called Pre-Implantation Genetic Screening (PGS) can be performed in conjunction with IVF. The PGS determines the genetic profile of the embryos before their transfer to the uterus.
Preventive - gynecological exam that must be done annually
Transvaginal ultrasound – imaging exam that allows the evaluation of the reproductive system and allows counting of antral follicles (AFC). The count of these small follicles is performed in the first 3 to 4 days of the menstrual cycle and assesses the ovarian reserve of the patient who wishes to become pregnant and her response to treatment. A low antral follicle count is related to greater difficulty with pregnancy. On the other hand, serial ultrasounds can establish the patient's ovulatory pattern.
Hormonal Tests - Follicle-stimulating hormones (FSH) and estradiol are tested on the second, third, or fourth day of the menstrual cycle. A high value of FSH and/or estradiol indicates that the chances of getting pregnant should be lower, especially in patients aged 35 years and over. Anti-Mullerian Hormone (AMH) levels can be requested and provide additional information on ovarian reserve. A decreased AMH level means a compromised ovarian reserve. High FSH levels, low AMH or low antral follicle count do not mean that there is no chance of pregnancy, but a lower chance of becoming pregnant and that more specific treatment is needed, especially for patients over 35 years of age. Age is the most important factor in pregnancy.
Blood tests to search for infectious and sexually transmitted diseases - hepatitis, HIV, HTLV, Zika, rubella, CMV, among others must be carried out before the treatment to become pregnant starts
Karyotype – a genetic test made from blood samples that determines the patient's chromosomal pattern.
Hysteroscopy - This minimally invasive procedure can be performed to assess or correct uterine structural problems such as endometritis and polyps.
Hysterosalpingography - During HSG, a special dye is injected through the vagina, fills the uterus and travels to the fallopian tubes. If this liquid leaves the end of the tubes, they are open (permeable). If the dye does not come out, the tubes are blocked. If the result is this, the doctor may order a laparoscopy to assess the degree of tubal involvement. In some cases of damaged or blocked tubes a surgical procedure can correct the problem. However, surgery does not guarantee that the tube, even if it is permeable, works properly.
Laparoscopy - This surgery is performed under anesthesia, in a hospital unit in a day clinic regimen (hospitalization for one day). During the procedure, the abdominal cavity, ovaries, fallopian tubes and uterus are directly observed.
Spermogram - To make this evaluation, a sexual abstinence of 3-5 days is required. The man collects the semen sample by masturbation, which is evaluated according to the following parameters: sperm volume (quantity), motility (movement) and morphology (appearance and shape).
Blood tests to search for infectious and sexually transmitted diseases
Often the factors that affect fertility are easily detected and corrected, but in some cases the diagnosis of infertility remains undetermined. After a thorough investigation, the specialist physician makes an assessment of the chances of success among the various treatment options. Side effects, costs, risk of multiple births and success rate are important when choosing treatment. Each patient is a unique universe and the chances of success vary widely. Obtaining pregnancy depends on many factors, especially maternal age and embryo quality.
Infertility is a medical condition that generates many emotional aspects. Feelings of sadness and anxiety can affect social life. It can be difficult to share these feelings with friends and family. But it is important to know that these feelings are common and described by patients who undergo human reproduction treatments. However, the sooner you seek help, the sooner the dream comes true.
ARTIFICIAL INSEMINATION - INTRA UTERINE INSEMINATION (IUI)
Process by which millions of sperm are injected directly into the uterus to promote a more efficient meeting between sperm and egg. Sperm are subjected to treatment in order to remove contaminating material and increase sperm motility and concentration. The fertilization of the egg by the sperm occurs naturally in the fallopian tube and the resulting embryo implants in the uterus.
IN VITRO FERTILIZATION (IVF)
An assisted reproduction method that involves removing eggs from the ovaries and fertilizing them with sperm in the laboratory. The resulting embryos are transferred after 2 to 5 days of incubation to the maternal uterus.
There are many factors that impede the union between sperm and egg. Thus, IVF tries to promote this union in the laboratory. Initially, IVF was used to treat women with obstructed or damaged tubes or without tubes. Currently, IVF is applied in many infertility conditions, such as endometriosis, sperm abnormalities or in cases of infertility with no apparent cause.
The steps of IVF are stimulation of the ovaries with specific medications, aspiration of eggs from the ovaries, fertilization of the egg with a sperm, culture of the embryos and embryo transfer to the mother's uterus.
During ovarian stimulation, medications are used that induce the growth of various follicles in the ovaries. Many follicles are stimulated, unlike a natural cycle where you only have one mature egg. This is because some of these eggs may not be fertilized or develop abnormally even in the IVF technique.
The timing of each step is essential in the treatment of IVF. The ovaries are stimulated by medications (usually FSH or HMG) and their growth is monitored by serial transvaginal ultrasound tests. Hormonal measurements are performed to assess the response of the ovaries to inducing drugs. Normally, estrogen levels increase as follicles develop and progesterone levels increase after ovulation.
Through ultrasound examinations and hormonal dosages, the specialist doctor determines when the follicles are ready to be aspirated. They usually require 8 to 14 days of hormonal stimulation. When the follicles reach the ideal diameter and hormone levels are compatible, aspiration of the follicles is programmed to obtain the eggs.
About 20% of cases can be canceled before aspiration of the eggs. Cycles can be canceled for a variety of reasons, such as the low number of stimulated follicles. Cancellation rates due to poor ovarian response increase with maternal age, especially after 35 years. When treatment is suspended due to poor ovarian response, drug alternatives can be used that increase the chances of response in future treatment. Currently, rare cycles are suspended due to ovarian hyperstimulation.
Follicular aspiration is guided by transvaginal ultrasound, a low-complexity procedure performed in an operating room, in the presence of an anesthesiologist. An ultrasound probe passes through the vagina with a needle that pierces the ovary and collects follicular fluid from each follicle. Eggs are captured from the follicular fluid by the embryologist at the IVF Laboratory.
Eggs isolated from follicular fluid are identified and classified in the IVF laboratory according to their maturity and quality. Each mature egg is inseminated by a sperm. Obtaining embryos can be done using the Conventional IVF technique in which sperm and eggs are placed in the same environment and fertilization occurs naturally; or fertilization can be done using the Intracytoplasmic Sperm Injection (ICSI) technique, in which a single sperm is injected into a mature egg. In the United States 60% of IVF cases are performed using the ICSI technique, while in Brazil 90% of clinics perform ICSI.
About 75% of mature eggs will fertilize. Embryos formed in IVF are kept in an incubator for 2 to 5 days. These incubators have temperature and atmosphere conditions similar to the tubes (37oC, 6.0% CO2, O2 and N2). Two days after follicular aspiration, the fertilized egg divides and becomes a 2-4 cell embryo. By the third day the developing embryo normally contains 6 to 10 cells. On the fifth day, a cavity forms inside the embryo and this becomes called the blastocyst.
Embryos can be transferred to the mother's uterus in 2 to 5 days after egg aspiration. Transfer is done without anesthesia, guided by ultrasound. A catheter is introduced through the vagina to the uterus where one or more embryos are transferred, according to the patient's age, following the rules of the Federal Council of Medicine:
Up to 35 years old - maximum 2 embryos
35-39 years - maximum 3 embryos
Over 40 years old - maximum 4 embryos
Cryopreservation is a technique used worldwide for freezing embryos, eggs and sperm. The cryopreservation method called vitrification has been associated with high rates of pregnancy.
Surplus embryos can be cryopreserved for a long time. There are reports of pregnancy with embryos frozen for 20 years. This option allows a new attempt at pregnancy without the need for a new treatment if the pregnancy did not happen in the first IVF; or a second pregnancy if the first treatment was successful and more children are wanted; or the donation of embryos.
In some IVF treatments, for medical reasons, such as the risk of ovarian hyperstimulation, all embryos are frozen and transferred to the mother's uterus in a later cycle.
The option of cryopreservation of eggs has become common nowadays, enabling women to postpone motherhood without reducing their chance of a future pregnancy.
Patients who will undergo cancer treatment can through this technique preserve their fertility. Men and women who will receive chemotherapy can freeze sperm and eggs for possible future pregnancy.
GAMETE AND EMBRYO DONATION
Widely spread in the modern world, the donation of gametes and embryos has been a practice adopted in several assisted reproduction treatments. Donation can be a choice in cases of poor oocyte or sperm quality or occurrence of genetic diseases, for example. Following strict confidentiality rules, the anonymity of the egg donor woman, the semen donor, or the couple who donate embryos is allowed. IVF treatment can be done with your own eggs and semen from a Semen Bank, you can "adopt" the eggs of an anonymous patient and the husband's semen or even receive embryos from another couple or from gametes of banks.
The characteristics of the semen donor (blood group, skin color, height, weight, eye and hair color, among others) are presented in a list provided by the Semen Bank. Semen samples are analyzed, frozen and kept in quarantine in the Semen Bank for 6 months, when they are retested for the presence of infectious and sexually transmitted diseases. Only samples with all negative tests are released for donation.
The Shared Ovodonation Program consists of treating two patients simultaneously: an egg donor and an egg recipient. These patients have in common the indication for an IVF treatment (obstructed tubes and age, for example), normal medical and genetic evaluation, negative tests for infectious and sexually transmitted diseases and common characteristics. The donor patient, under 35 years old, donates part of her eggs to another patient (RECEPTOR) who pays for her treatment. Eggs can also be purchased through Egg Banks. Just like semen donors, egg donors undergo a genetic evaluation and careful tests to rule out the presence of infectious and sexually transmitted diseases.
IVF treatments that generate surplus embryos are the source for embryo donation. Pregnancy materialized in the treatment of IVF and the time has come to decide the fate of the surplus embryos: anonymous donation would be a great option!!!
There is an important factor to consider when giving: doing good. Donation is often motivated by helping someone who doesn't even know themselves, but who has the same dream of motherhood.