It is so difficult to get pregnant?
When couples have sexual intercourse during the fertile days in the absence of obvious problems, the possibility of achieving a pregnancy in one month does not exceed 25%. So it is not strange that even without infertility problems it can take several months to conceive, and this expectation can become longer when any problem causes a sub-optimal fertility. In fact conceiving is pretty easy at a very young age, regardless of genetic, somatic and metabolic variables that become more and more important in reducing fertility over the years (especially after the 30 years of age). In other words, it is hard to find big differences in the probability of pregnancy of a 20 year-old woman, while these differences become significant in 30 year-old women and can be enormous when women are 40 years old.
How many infertile couples are there?
Infertility is definitely a growing phenomenon, at least in the western world, mainly because of the social changes such as the postponement of the age of marriage and of childbearing. The latest epidemiological data indicate that 1 of 5 couples in Italy has difficulties in having children. Almost half of these couples require a medical opinion to obtain pregnancy. Unfortunately, that’s not always an expert’s opinion, and this may lead to a delay in appropriate and effective interventions. Only a third of the couples is referred to a specialist of Reproductive Medicine. International data on assisted reproductive activity, periodically pubblished, show a continuous growth of the assisted reproductive techniques, since the first success of Robert Geoffrey Edwards, in Britain, more than 30 years ago, with the birth of Louise Brown, today already mother in turn. The main underlying causes of this phenomenon are the postponement of childbearing, the spread of sexually transmitted diseases that can impair reproductive function in women and in men, even when asymptomatic, the eating habits that lead to excess body weight up to obesity, the environmental pollution and cigarette smoking, which definitely has a negative impact on ovarian function. Traditionally, a healthy couple will take about a full year to become pregnant, so they can wait this time frame before referring to a specialist. Anyway this arbitrary limit of time is reasonable only if the woman is younger than 35, if intercourses are regular, in absence of ideases impairing fertility, and when menstrual cycles are almost regular. If not, it is necessary to refer promptly the couple to a specialized center.
When it is appropriate to turn to a doctor?
When fertility problems exist or are suspected it is useful to have a talk with the specialist of Reproductive Medicine, even just to be reassured about the reproductive status of the couple. Even couples with children may have some infertility problems. It is also possible to have difficulties to have a second child despite not having changed partners, because of miscarriages or diseases after the first pregnancy or when the research period was long already for the first pregnancy. We have to keep in mind that even a rare event (such as a pregnancy in couples with fertility problem) can occur at any time, even after short period, but it can not happen a second time just as easily. Fertility always depends on the couple and not on the individual. In other words, it is not advisable to consult a doctor to know your fertility potential, without your partner.
How to choose the center and/or doctor to turn to?
It is necessary to ask yourself the right questions to be able to choose the right center. The word of mouth can have its value: if we know someone who felt good, it can predispose you well to the structure. The proximity of the center to your home or your work can make it easier to reach the center, and it can be useful because of the frequency of examinations required during treatment. The availability to be received shortly and the costs are other important aspects. But these are not the main criteria. The results of the Centre represent the main point. You can see whether a center "works well" considering the number of cycles performed and the pregnancy rates of the previous years. These results must be provided and explained by the doctor that takes charge of you. These statistics are the only parameter to make a comparison between different structures. Additional quality assurance are the quality certifications (eg ISO certification), the scientific research activity (documented by specialist publications) and the collaborations at international level. Finally the quality of interaction with the physicians and staff is a crucial point for patients.
How important is the impact of age on fertility?
The age, especially woman’s age, is pivotal for the couple's fertility. Ovarian reserve decreases exponentially with ages, especially after the age of 35 years. That’s not only a quantitative fact (the number of eggs contained in the ovaries reduces with time) but mostly a qualitative fact, regarding the genetic structure of the oocytes that tend to have more frequently abnormalities leading to an increased risk of failed fertilizations, failed implantations, abortion or fetuses with chromosomal abnormalities (such as Down's syndrome). Oocytes are extremely complex compared to spermatozoa and can only be created before the birth to be stored in the ovaries. From birth until menopause eggs can only be "consumed" and not produced ex novo. It is clear that a 38 year-old oocyte will have had more time to undergo damages than an oocyte that has waited only 20 years before reaching ovulation. Moreover the incidence of myomas and endometriosis increases with woman's age (and with the number of menstrual cycles), these benign disorders can cause obstetric complications and a reduction of ovarian reserve, respectively. Even the semen is affected by the passage of time, but in a more nuanced way and from a more advanced age. As the sperm renews completely every three months, it does not present a higher risk of chromosomal abnormalities with increasing paternal age.
Does body weight play an important role?
Body weight plays an important role in female fertility. Alterations of the weight (both overweight and underweight) may impair fertility resulting in anovulatory cycles and exposing women to serious diseases during pregnancy such as preeclampsia and diabetes. When a hormonal stimulation is required, the dose of medication to be used will have to be increased if the woman is overweight. We refer to body mass index that relates body weight in kg to height in meters (BMI - body mass index = kg / m2). A BMI between 18 and 25 is considered normal. Overweight is defined as a BMI between 25 and 30 and above 30 it is called frank obesity. With the increase of BMI there is a reduction of the probability of pregnancy and an increased risk of abortion. This does not mean that all obese women are infertile. The distribution of body fat also important. Typically the accumulation of fat in the abdomen is worse than the accumulation at the level of the buttocks and thighs. Severe thinness can determine anovulatory cycles or even the disappearance of the menstrual cycles. Regardless of the reason that caused the weight loss, finalistically it can be said that nature has decided to prevent conception in women with poor metabolic reserves to support the pregnancy. For all these reasons, attention to body weight and healthy eating habits are of primary importance for women looking for a child: the correction of the diet by a specialist is essential for those who have weight problems.
Someone told me about PCOS, is it a disease?
No! The polycystic ovary syndrome is not a disease but a particular ovarian conformation characterized by the presence of several follicles (each follicle is the container of an oocyte) arranged "in a rosary" inside the ovaries that are larger than the average. Women with this type of ovary frequently have longer and irregular cycles with numerous anovulatory cycles during the year, they show a tendency to take weight easily, they have high levels of insulin in the blood and they tend to develop sugar intolerance. They often have acne and hair excess in typically male body areas (face, back, abdomen, thigh and arm root). When the ultrasonographic appearance of polycystic ovaries is associated with these symptoms, it is called polycystic ovary syndrome. The dosage of circulating androgens often shows a higher level, just as it is easy to find a slight increase in prolactin. The assessment of plasma fasting glucose and insulin can be useful to complete the clinical picture. When insulin increases, the ovarian function is often inhibited. A support therapy to reduce circulating insulin levels may be recommended. The estro-progestinic pill can regulate the cycle of women with polycystic ovaries, but it certainly can not "heal" the patient. The problem of menstrual irregularity and other problems will reappear at the suspension of the estrogen-progestin therapy. The diet can help to improve menstrual cyclicity. A diet lacking in quick absorption sugars (sweets, soluble sugar, sweetened beverages such as tea and fruit juices, sugary fruits like bananas, grapes, apricots etc.) improves metabolism while reducing circulating insulin levels and improves ovarian function with an ovulation facilitation.
What is semen analysis? What is the capacitation in vitro test?
The examination of the seminal fluid is absolutely essential to assess any fertility problems of a man. However, it should be emphasized that a "normal" semen analysis does not guarantee the possibility of conception, as well as an altered semen analysis is not a synonymous of "infertility." The most common abnormalities detected in a semen analysis are: the asthenozoospermia, that is an abnormality of sperm motility; the teratozoospermia, that is an alteration of the shape of the spermatozoa which makes them unable to fertilize the egg; the oligozoospermia, that is a reduction in the number of spermatozoa below the considered "normal threshold" for conception. These three anomalies may be associated in the so-called "oligo-terato-asthenozoospermia", abbreviated as OTA. An absolutely serious framework of infertility, only detectable with semen examination, is azoospermia, ie the complete absence of sperms in the semen. Since sperm production by the testis is not regular, but may vary from day to day and according to particular clinical conditions, it is always prudent to perform at least two seminal exams at the distance of a month of each other before to reach conclusions about infertility. The uro-andrological assessment of seminal examination will relate the results to clinical and objective data.
What is intrauterine insemination?
The intrauterine insemination is the introduction of the seminal fluid, suitably prepared, inside the uterine cavity through a thin catheter that passes through the cervical canal. It represents the first level of care with timed intercourse. This technique provides a chance of pregnancy of 12-15%. It is indicated for those couples in which at least one tube is patent, the ovarian reserve is good and the semen is normal. As well as for timed intercourses, ovarian stimulation is aimed to have one or two follicles growing, and there is an ultrasound monitoring of follicular growth. In case of multiple follicular response there can be a twin pregnancy. The doctor will inform the couple of that opportunity, and together they will evaluate whether to proceed with the treatment or not. Usually when more than three follicles are growing, the stimulation is stopped because of the risk of multiple twins. The limit may be even lower for some couples on medical or subjective indication, and this will be discussed case by case. Intrauterine insemination is performed only once per cycle, about 24-36 hours after ovulation induction. It is also useful to associate the normal sexual intercourses with the insemination itself. It is indeed advisable an abstinence of 2-3 days before intrauterine insemination to allow greater concentration of sperms in the semen. Abstinence, however, should not be extended beyond five days because of the reduced viability of ejaculated sperm in that case. After insemination, the woman can return to normal daily activities. It will be useful to have luteal phase support with the administration of progesterone for about two weeks after insemination.
What is in vitro fertilization?
IVF (in vitro fertilization) implies the meeting between the egg and the sperm in a laboratory. It is necessary to retrieve surgically oocytes from the ovary. A reasonable number of oocytes is necessary to get good results. As every woman normally produces one egg per menstrual cycle, an hormonal stimulation with gonadotrophins is necessary to get more mature oocytes at the same time. Gonadotrophins are molecules produced by the pituitary gland, a gland at the base of the brain; in the hormonal stimulation we use higher doses compared to the physiological ones. A different treatment will be scheduled for every patient, according to her characteristics and indications to IVF. Duration of therapy can vary from 15 days to one month. Patients are absolutely autonomous in the administration of therapies, which are mostly administered subcutaneously, so the first part of the treatment takes place at home. A greater commitment is required during the last week of treatment because it is necessary to monitor the proper development of the follicles via blood samples and ultrasound scans. Finally the day of oocyte retrieval is determined. The male partner will produce a semen sample on the same morning of oocyte retrieval; it will be treated to select the best quality sperms to fertilize the oocytes. The sperm will be placed in contact with the eggs in special incubators that create a controlled environment favourable to fertilization, that is the entrance of the sperm into the oocyte. The next day, the oocytes will be examined under a microscope to assess whether fertilization occurred. The fertilized eggs are then stored in an incubator at least for two days up to a maximum of five days, before being transferred into the uterus of the patient.
What is ICSI?
It stands for Intra Cytoplasmatic Sperm Injection. It is a useful technique when there is a severe seminal deficit that reduces the probability of spontaneous fertilization of the oocyte. The treatment for the woman is identical to the one for classical IVF, but the way of bringing together egg and sperm changes. Once the eggs are retrieved, the biologist injects a single sperm into the cytoplasm of an egg through a microneedle. The procedure is performed under a microscope with a special equipment which limits the accidental movements and that makes the drilling of the oocyte cell wall extremely precise. The chances of pregnancy with this technique are similar to those of the classical in vitro fertilization. On average it is around 30-40%, with variations depending on the age of the woman and the severity of the male factor.
How do you retrieve eggs?
The egg retrieval is performed under ultrasound guidance, with a needle placed on a rail positioned on transvaginal ultrasound probe. With the ultrasound we can see the ovarian follicles as anechoic (black), rounded areas. We puncture every follicle of adequate size and aspirate the liquid in its interior. The oocyte is inside the the follicular fluid, surrounded by some layers of cells (granulosa cells). The complex oocyte-granulosa cells is visualized by the biologist to real-time microscope during the ovum pick up. The oocyte retrieval is performed in a surgical room adjacent to the laboratory to minimize the exposure of oocytes to air. The aspiration of follicles has a duration of 10-20 minutes, depending mainly on the amount of follicles to be aspirated and to the position of the ovaries. It can be performed in local anesthesia, that is practiced at the two sides of the cervix with local anesthetics similar to those used by the dentist. Intravenous sedation can also be practiced to raise the pain threshold and lower the consciousness. Normally this procedure is well tolerated and almost painless. After surgery the woman is kept under observation and discharged within a few hours. The patent should have absolute rest for the whole day, even at home.
How do you perform embryo transfer?
Once applied the speculum, the cervix is cleansed with sterile saline and a few cotton balls. We then insert a small flexible plastic catheter within the cervix to reach the uterine cavity where the embryos are deposited. Ultrasound scan can help us to place the embryos in the part of the uterine cavity that provides the highest pregnancy rate. The embryo transfer is normally atraumatic and does not require any anesthesia. In some cases, it may be necessary to use a more rigid catheter to overcome the cervical canal and uterine cavity to access or manipulate the cervix with forceps to modify the curve. In these cases embryo transfer may be a bit annoying. In some exceptional cases, especially when there was a previous cervical surgery, the embryo transfer can be particularly difficult and require a cervical canal dilation prior to embryo transfer.
Is IVF pregnancy the same of a normal pregnancy?
Yup! In any case it is appropriate that the gynecologist who takes charge of the pregnancy and the team be present for the delivery are informed that the pregnancy was obtained thanks to assisted reproduction techniques. During pregnancy normal malformations screening tests such as integrated test or combined test during the first trimester and ultrasound morphological screening during the second trimester can be made. In this case it is important to specify the use of assisted fertilization technique as hormone levels are different from those of a spontaneous pregnancy and this must be considered in the algorithm that calculates the risk for this particular pregnancy. When appropriate, diagnostic tests such as chorionic villus sampling in the first trimester or amniocentesis in the second trimester may be carried out. These examinations are able to detect the majority of fetal malformations and chromosomal abnormalities. Invasive diagnosis is recommended for women above the age of 35 and for those couples with severe asthenozoospermia in the male partner. The delivery will take place with the same timing and procedures of a spontaneous pregnancy.
Children born with assisted reproductive technology have higher risk of malformations?
No. There is an international monitoring that documents malformations apparatus for apparatus malformations and tumors reported in fetuses, infants and children from both spontaneous pregnancy or IVF. There are numerous publications reporting the epidemiological data from several large series. Globally there is not an increased risk of malformations in children born from in vitro fertilization than in the general population. Only in case of severe seminal deficits, there may be an increased risk of chromosomal abnormalities in comparison to general population. This increase seems to be related to the sperm quality rather than to the ICSI technique itself. Recent studies failed to find an increased risk of fetal diseases or fetal mortality in IVF pregnancies compared to spontaneous pregnancies, when correcting the results for the mother’s age, twinning and previous pregnancies. Obstetric risk may increase in presence of pre-existing risk factors or when maternal age raises, conditions often associated with infertility. In these pregnancies the increased risk of maternal and fetal pathologies depends on previous conditions and not on the conception technique used.