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  • What about success rates of IVF?
  • What is the duration of one IVF or ICSI cycle?
  • What is Egg-donation?
  • What is Cryopreservation?
  • What is TESE or PESA?
  • What does sperm preparation mean?
  • How and why are embryos frozen?
  • What is assisted hatching?
  • Why do not all embryos implant in the human?
  • How can we improve the implantation rates of human embryos in human IVF?
  • What about the transfer of only one embryo to reduce the incidence of multiple pregnancies?

  • What is the general progression of infertility treatment?

    A variety of procedures can be used to diagnose the cause of infertility in a couple; these range from simple blood tests to more complicated analytical methods. In any case, diagnosis is a crucial first step to determine the appropriate therapeutic path that should be followed. In addition to the cause itself, other factors, such as the age of the woman, or problems shared by both partners, might also influence the choice of treatment.

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    What treatment options do infertile couples have?

    Several options are offered to couples depending on the type of infertility that has been diagnosed. The vast majority of female patients are successfully treated with the administration of drugs such as Clomiphene Citrate, Bromocriptine or Gonadotrophins. Surgery can also be a means to repair damage to the reproductive organs, such as those caused by endometriosis and infectious diseases. Treatment options for male infertility also include the administration of drugs, surgery and assisted reproductive technologies, such as Intracytoplasmic Sperm Injection (ICSI). Drug therapy and surgery have proved very successful for specific types of male infertility. However, in a great number of cases, the reason why men have fertility problems remains unexplained and the treatment methods applied are empirical. Some patients nevertheless require more complex medical intervention.

    Assisted reproductive technologies (ART) refer to several different methods designed to overcome barriers to natural fertilization such as anatomical problems (e.g. blocked fallopian tubes). One of these techniques, in-vitro fertilization (IVF), has now been practiced for more than 15 years. Overall, the estimated number of infertile patients currently treated by ART is around 20%.

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    How successful is infertility treatment?

    When talking of success rates for any type of infertility treatment, one should bear in mind that the average chance to conceive for a normally fertile couple having regular unprotected intercourse is around 25% during each menstrual cycle. It is estimated that 10% of normally fertile couples fail to conceive within their first year of attempt and 5% after two years. Comparable to normal fertility rates, effective treatments can be expected to have, on average, up to a 25% success rate per cycle of treatment, and may therefore need to be repeated several times before a pregnancy is achieved.

    Simple ovulation induction to compensate for hormonal imbalances has a very high success rate; more than 80% of women suffering from such disorders are likely to conceive after 6 to 12 cycles of treatment with drugs such as Clomiphene Citrate or Gonadotrophins. The pregnancy rates may be increased if this is combined with Intrauterine Insemination (IUI)

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    Are there particular factors influencing the success of a treatment?

    In any type of infertility treatment, important factors need to be taken into account when referring to success rates. The age of the woman and the duration of the couple's infertility are likely to influence the success of treatment. In women, fecundity decreases as age increases, particularly after 40 years of age. When the woman is being treated, her chances of conceiving can be lessened if her partner also has infertility problems (e.g. poor quality sperm).

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    Are there particular health risks for women undergoing infertility treatment?

    Along with their intended benefits, drugs used to treat infertility may on occasion cause side effects. In ovulation induction, close monitoring of follicular growth is crucial to ensuring successful treatment.

    Monitoring techniques (such as ultrasound scan and blood tests) and adequate use of treatment protocols help the physician to avoid ovarian hyperstimulation syndrome (OHSS) and minimize the risk of multiple pregnancy. Current treatment protocols have been designed to reduce the risk of multiple births and OHSS.

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    Ovarian Hyperstimulation Syndrome (OHSS) is a side-effect that can occur during infertility treatment with ovulation inducing drugs. Symptoms of this syndrome may include ovarian enlargement, accumulation of fluid in the abdomen and gastrointestinal disorders (nausea, vomiting, diarrhea). Severe cases of OHSS are however very rare (1-2% of cases). One may have to admit the patients in an Intensive Care unit. Rarely, she may need to undergo abdominal tap procedure, to remove fluid from her abdomen. Very rarely, she may need more intensive therapies such as dialysis, or respirator. In order to prevent or reduce the severity of OHSS, intravenous albumin may be given at the time of egg pickup during IVF/ICSI procedure.

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    Multiple births

    Multiple births occur more frequently after infertility treatment than in the normal population. About 80% of pregnancies achieved following simple ovulation induction with Gonadotrophins result in single births, the remaining 20% being multiple pregnancies, mostly twin pregnancies. New treatment regimens carefully adapted to the patient's response help to decrease the risk of a multiple pregnancy.

    After IVF, one pregnancy out of four is multiple (20% twin pregnancies and 3-4% triplets. In IVF centers, physicians now frequently choose to replace a maximum of three embryos after fertilization, to further reduce the chance of multiple births. Alternatively, many units are going in for blastocyst culture, especially if there are 3 or more 8 cell embryos available for transfer on day 3.

    In case of triplets or more, one can offer the procedure of Fetal Reduction, to the patient. In this, with the help of sonography, a thin needle is passed into the fetus , and drugs are injected to stop the fetal heart. Care is taken to see that at least two intact fetuses are left behind. This is a relatively simple technique, with minimal side effects. However some patients may avoid this technique for religious or personal reasons.

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    Local side effects

    Common local side effects experienced by patients who receive Gonadotrophins by intramuscular injection include skin redness, swelling and bruising. Pain and discomfort sometimes reported after intramuscular injections are now likely to be lessened with the availability of a highly purified follicle stimulating hormone preparation which can be administered subcutaneously. Nowadays Gonadotrophins produced by recombinant DNA - or genetic engineering - techniques are available for administration by subcutaneous injection.

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    Can ovulation induction increase the risk of ovarian cancer?

    Ovarian cancer is a rare disease; the chance of a young woman developing an ovarian malignancy during her lifetime is lower than 1.5%. A number of factors have been found to increase the risk of ovarian cancer, including genetic predisposition and dietary habits. Scientific studies carried out in the last few decades have demonstrated that infertility itself is a risk factor for ovarian cancer.

    There is evidence that each pregnancy reduces the risk of a woman contracting ovarian cancer (this risk could be reduced by more than 25% by a first pregnancy). No epidemiological study has ever established a causal link between ovulation promoting drugs and ovarian cancer. An extensive study on this issue, reporting on more than 2,600 women treated between 1964 and 1974 and followed for an average of twelve years, found no association between ovulation inducing drugs and ovarian cancer.

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    What about the health risks for children born following infertility treatment?

    Regarding children born following treatment with ovulation promoting drugs, the incidence of birth defects has never been found to be higher than that in the normal population. The same goes for babies conceived after IVF. The incidence of malformations is around 2%, which is comparable to that of babies born naturally, without any treatment.

    In patients undergoing ICSI the incidence of malformation is around 2.7%. If the father has a low count, there is a chance that the male child, born following ICSI may also inherit the defect.

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    How important is counseling to the patient undergoing infertility treatment?

    The physician helps the infertile couple find the most appropriate therapeutic path to overcome barriers to conception, but before a treatment is started, patients need to be aware of all its aspects, including its constraints. Beyond the medical expertise, infertile couples are also looking for counseling and support. From a psychological point of view, infertility is often a hard condition to cope with. During treatment and before a pregnancy is achieved, feelings of frustration or loss of control usually experienced by the infertile couple are likely to be exacerbated. Management of infertility includes both the physical and emotional care of the couple. Therefore, support from physicians, nurses and all people involved in treating the infertile couple is essential to help them cope with the various aspects of their condition. Offering counseling and contact with other infertile couples and patient associations can provide help outside the medical environment.

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    What is timed sexual intercourse?

    To increase the chance on getting pregnant spontaneously, timed sexual intercourse is recommended. This means that sexual intercourse, or coitus, has to take place around the time of ovulation, which is the most fertile period of a woman. To detect the approximate time of ovulation a temperature curve of several menstrual cycles can be made. The woman takes her body temperature each morning before getting out of bed, starting on the first day of the menstruation until the start of a new period. The body temperature rises around 0.5 degrease Celsius after the ovulation. This is mostly about 14 days after the first day of the period and when no pregnancy occurs the temperature drops to normal again, with pregnancy the temperature stays high. One can also use urine or saliva tests to detect the ovulation.

    Alternatively, one can use a serial ultrasound monitoring to follow the development of the follicle and subsequent rupture which indicates ovulation. The time of ovulation can sometimes vary a few days each month, even in a regular menstrual cycle. Also, if the circumstances are right, sperm can live inside the women for a few days and sperm quality can decrease with high sexual activity. Therefore, it is best to have intercourse 3-4 days before the expected ovulation and every other day until 2-3 days after the expected ovulation with no necessity for higher frequency.

    When tests are used to detect ovulation it is advised to have sexual intercourse on the day of a positive test.

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    What is embryo reduction?

    Assisted Reproductive Therapy (ART) has caused an increase in multiple pregnancies. Especially in ovulation induction and Intra Uterine Insemination, this situation is encountered frequently. In order to prevent the risk of severe premature birth and handicaps as well as risks for the mother, embryo reduction is sometimes performed: The amount of embryos in the uterus are reduced and the remaining pregnancy has more chance of normal development and delivery. Of course this is not an easy decision for both patient and doctor. With careful guidance of the patient during treatment and good counseling when the patient is at risk for a large multiple pregnancy, many triplets or higher pregnancies are already avoided.

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    What is reproductive surgery?

    Reproductive surgery is a subspecialty that treats anatomical abnormalities interfering with normal reproductive function. Advanced reproductive surgery requires meticulous surgical technique for optimal results, including rapid patient recovery and avoiding the need for routine hospitalization. Reproductive surgeons treat tubal obstruction, endometriosis, uterine fibroids, scarring of the ovaries or other pelvic structures resulting from pelvic inflammatory disease (PID) in the female, and varicocele and vas obstruction in the male as well as other abnormalities.

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    INSEMINATION Is Intra Uterine Insemination suitable for every infertile couple?

    No. In Intra Uterine Insemination (IUI) semen is directly put into the uterus. It is a technique used for couples with fertility problems based on specific causes. These causes are:

    Cervical hostility: This means that the cervix is not permeable for semen shown after the Post Coitum Test.
    Idiopathic subfertility: No cause has been found for the inability to conceive
    Male subfertility: The sperm quality is decreased. Clinics use different ranges for sperm count in which they perform IUI.
    Sperm Antibodies: Inability for vaginal ejaculation with decreased sperm quality, for example in men with retrograde ejaculation or spinal cord injury.

    IUI can be performed either in a spontaneous ovulatory cycle (cervical hostility) or in a cycle with ovarian stimulating hormones (idiopathic sub-fertility and male sub-fertility/sperm antibodies). The stimulation is mostly done with Clomiphenecitrate or Gonadotrophines.

    Nowadays, the indication may be relaxed to include all cases where routine treatments have failed. These patients can be given 3-6 cycles with Gonadotrophin stimulation with Intrauterine Insemination, before they opt for IVF/ICSI.

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    IVF/ICSI What about success rates of IVF?

    Overall, success rates for IVF have steadily improved over the last ten years. Birth rates for IVF vary according to the expertise of the centers practicing this technique. However, centers in Europe have reported pregnancy rates after one cycle of IVF equal or superior to 25%. In 1993, the French IVF registry (FIVNAT) reported a pregnancy rate of 25.4% per embryo transfer on a total of 23,025 oocytes retrieved.

    Based on such results, after three to four cycles of IVF, a woman under 40 whose partner does not have any fertility problems could reasonably expect to give birth. Again, in general, success rates may vary from one center to another, since they are influenced not only by the level of expertise of the medical team but also by the characteristics of the patients treated. A clinic treating a large number of women over 40 is likely to report lower success rates than a clinic having a majority of patients under 35. This is because the success rates are better in women who are less than 35 years of age.

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    What is the duration of one IVF or ICSI cycle?

    One complete IVF or ICSI cycle takes approximately six to eight weeks. First, the normal menstruation cycle of the woman is down regulated by injection or nasal application of specific hormones each day. This part of the cycle can vary from a few days to several weeks. When the ovaries have become inactive, shown on ultrasound control and laboratory findings, the stimulation of the ovaries start by muscular or subcutaneous injections of hormones. The mean stimulation period is 12 days, depending on the reaction of the ovaries. The ovum pick up takes place within two days after stopping the stimulation. Now the real IVF or ICSI follows in the laboratory. When fertilization occurs, embryos are transferred into the uterus after two to four days and drugs supporting the uterus are given. After approximately 15 days a pregnancy test will show whether the IVF treatment has been successful or not.

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    What is Egg-donation?

    Women with no, or not properly working ovaries can, in some cases, get pregnant through egg donation. In this procedure another woman, mostly a relative or good friend, will be the egg donor. This woman will have an IVF stimulation and ovum pick up. After the ovum pick up the collected eggs will be fertilized with sperm of the partner of the recipient woman i.e. donor acceptor. The embryos are then transferred in uterus of the donor acceptor. If a pregnancy occurs, the donor acceptor and her partner will have a child which is only biologically, half their own.

    In recent times, another concept called egg sharing , has also become very popular.

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    What is Cryopreservation?

    Cryopreservation means preserving in a frozen situation. The best-known Cryopreservation is of semen. This is mostly done in case of cancer of the testicles before treatment of the cancer. Furthermore Cryopreserved semen is used in donor insemination. It is also possible to freeze fertilized eggs after IVF or ICSI. If more embryos are left after an IVF or ICSI procedure they can be frozen and transferred another time. In this way there is a larger chance on a pregnancy while only one IVF or ICSI cycle is performed. For human oocytes Cryopreservation is much more difficult. Only in very few experiments this is done successfully. The attention of researchers now is on developing a way to freeze ovarian tissue and after thawing, to obtain the oocytes in it. This procedure is not yet fully refined but when it is, it can offer great opportunities in the future. We at the Babies And Us Fertility center have started doing preliminary research work in this area.

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    What is TESE or PESA?

    TESE: Testicular Sperm Extraction Sperm collected out of the testicles after operation. PESA: Percutaneous Epididymal Sperm Aspiration Sperm collected out of the epididymis by simple aspiration, without opening the skin

    TESE or PESA is a technique developed for patients with no sperm cells in their sperm due to an undeveloped or obstructed spermatic cord. The cause of obstruction can be a former sterilization, an infection of the epididymis or congenital absence of vas deferens. When the testicles make no sperm cells at all, of course TESE or MESA is not possible. If sperm cells are obtained, an ICSI procedure (Intra Cytoplasmatic Sperm Injection) will follow.

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    What does sperm preparation mean?

    Spermatozoa are ejaculated in the seminal fluid during intercourse or masturbation. During assisted reproduction the spermatozoa are extracted from the semen by a series of processes - centrifugation and washing, layering (to select the active sperm and leave the immotile or dead sperm behind) or selecting the best sperm by making them swim through a denser medium (Nidacon Puresperm or Spermgrad) and using those that succeed.

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    How and why are embryos frozen?

    Human embryos can be stored very successfully by being frozen and stored in liquid nitrogen. An estimated 15-20,000 babies have been born as a result of the freezing technology. Drug-induced stimulation of the ovaries, resulting in super ovulation, leads to an excess of embryos being created that can't all be transferred to the uterus at the same time. The good quality excess embryos can therefore be stored by freezing for transfer to the uterus at a later date. It should be noted that poor quality embryos do not withstand the freezing process that well, and hence are not generally frozen. This technique allows couples to have more attempts at IVF without the need for the woman to have to undergo another stimulatory cycle of IVF for egg collection.

    The success rates following transfer of frozen thaw embryos is in the region of 10-15 % - not as good as the fresh cycle success rates. In some countries freezing of embryos is restricted or banned (e.g. Germany and Switzerland will only allow freezing of the zygote - i.e. before the first cell division of the fertilized egg).

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    What is assisted hatching?

    Assisted hatching (AH) may help couples who have had many attempts at assisted reproductive procedures without success. It is a technique which helps the embryo implant in the endometrium. Embryo implantation is one of the greatest barriers to success in In Vitro Fertilization (IVF) cycles. When embryos are replaced into the woman's uterus, they are covered by an outer coating called the Zona Pellucida. Once the embryo is in the uterus, this "shell" must dissolve in order for the embryo to be able to "hatch", a necessary step for implantation. In certain situations, this step is less likely to naturally occur: in women 38 years and older, women with elevated serum FSH levels, and women who have failed to achieve a pregnancy in a prior IVF cycle) and in patients with AH, a microscopic glass tube is used to make a small defect in the zona using a very small amount of acid solution to dissolve the outer coating of the embryo. Nowadays this hole is created with the use of a laser beam.

    Babies and Us has already performed more than 300 cycles of Laser Hatching with very good results. Assisted hatching is done on the third day after egg retrieval, and embryos are immediately replaced into the uterus. It has been suggested that treating women with steroids (to suppress the mother's immune system) and antibiotics (to counteract any infections in the uterus) may be beneficial when carrying out assisted hatching. These medications are only given for four days, starting on the first day the eggs are collected.

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    Why do not all embryos implant in the human?

    After IVF, as after spontaneous conception embryos are susceptible to chromosome abnormalities. The egg or the sperm may have born the anomaly to start with, but at each cleavage division, mistakes may happen that lead to abnormal daughter cells in the embryo. These abnormal cells may fragment and get lost to the embryo. In case the embryo loses too much cells, its abilities to progress until the blastocyst stage and to implant may seriously be hampered and no pregnancy will follow. Actually the relatively low implantation potential of human embryos is an example of natural selection, which is very efficient in eliminating abnormal concept uses.

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    How can we improve the implantation rates of human embryos in human IVF?

    We cannot. All we can do is try to select the better ones so that the transfer will lead to a higher pregnancy rate. Some centers are experimenting with embryo biopsy and Aneuploidy screening to select the genetically soundest embryos. Other centers choose to culture the embryos to a later stage (the blastocyst stage) to select the best ones, and indeed both strategies seem to lead to higher implantation rates. These strategies, however, work only if a sufficient number of embryos are available. The major problem are still couples in whom only a low number of embryos can be obtained, since no selection can be performed there and the pregnancy rates will still remain low.

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    What about the transfer of only one embryo to reduce the incidence of multiple pregnancies?

    It seems to work, at least in a selected group of good prognosis patients. In this group (about one quarter of all couples) where the female partner is young (<35 yrs), possibly has been pregnant before and who are undergoing their first IVF attempts and where good quality embryos are available, the elective transfer of a single embryo leads to very acceptable pregnancy rates, similar to the ones in control patients undergoing double embryo transfer. However, no twin pregnancies are occurring, which is a major advantage in terms of neonatal outcome. Unfortunately, not all patients are good candidates to this approach and more clinical trials have to be carried out to investigate the possible wider use of elective single embryo transfer.

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