Introduction
You are now ready to try for a pregnancy. You are in a rush to have a child. You have waited a long time until everything is favourable to welcome a baby. You finally have the ideal partner, a stable job or perhaps a new home. After several months of trying; nothing. You don't worry and continue to try, paying a little more attention to your time of ovulation. After six months of trying, you are worried. After all, it seems that for all your friends, it worked at the first try. You become annoyed by questions from your friends and family. More months pass, the arrival of each period is more and more difficult. You start to ask yourself questions. Is it because I am too stressed? Perhaps it's because I am thinking about it too much? And does one of us have a problem? Is it him or me?
After a year of unprotected sexual intercourse, approximately 85% of couples will have conceived. Even amongst those who do not conceive the first year, 50% will become pregnant during the second year of trying. Therefore, for a woman of less than 30 years of age it is reasonable to wait for more than a year before commencing investigations for potential causes of infertility. On the other hand for an older woman or if the male partner or female partner show risk factors for infertility, investigations should be started sooner.
The physician with whom you consult at OVO fertility clinic will firstly look for, and then, if possible, treat any causes of infertility. Most women will become pregnant following evaluation and appropriate treatment. Your medical team will give you information, respond to your questions and attempt to reassure you. A psychologist will also be available to help guide you through this difficult period in your life.
Causes of Infertility
Ten to 15% of couples suffer from infertility, which is approximately 330 000 couples in Canada. This is actually a reduction of fertility in 84% of couples, with 10% sterility for female reasons (blockage of the fallopian tubes on both sides) and 6% sterility for male reasons (total absence of sperm.) The three principle causes of a reduction in fertility are male factor, i.e. an abnormal semen analysis (30 - 40%), pelvic disorders such as disease of the tubes or endometriosis (30 - 40%) or problems with ovulation (15%). The reason of infertility will be unexplained in 10% of couples. In a third of couples we will find a problem only with the male partner, a third with the female partner and for the other couples there will be a problem with both the male and female partner.
Basic investigations consist of verifying whether there is ovulation in the female partner, a semen analysis for the male partner, and finally to evaluate if the tubes are blocked or not using a hysterosalpingogram (a radiological procedure). Your physician will also check whether or not you are immunised against rubella and if not, offer you the vaccination. We suggest that you take folic acid (0.4mg per day) with the goal of reducing the risk of neural tube defects in the baby. We also encourage you to stop smoking cigarettes since it is toxic for the eggs and sperm and contributes to infertility. Marijuana, cocaine and excessive consumption of alcohol can also affect fertility.
What is infertility?
Infertility is defined as an inability to conceive after 12 months of unprotected sexual intercourse. This definition suggests that infertility and fertility will be a problem of all or nothing. The chances of spontaneous conception are often under-estimated. Therefore, a couple who have not conceived after a year of trying are infertile and this insinuates that it will be necessary to have medical treatment in order to conceive. In fact, becoming pregnant is a question of chance dependent on several factors. When there are regular sexual relations, a new chance of conception occurs each menstrual cycle. The rate of fertility per month is around 20% and is 6% to 8% even amongst couples with up to three years infertility if the woman is less than 30 years old. This monthly rate corresponds to a chance of pregnancy of 40 to 60% a year depending on the number of year's infertility. Even if the chance of pregnancy is low, due to a long period of infertility, a severe male factor, or advanced maternal age, there is still a chance of spontaneous pregnancy.
Male Factor Infertility
In our questionnaire we are looking for a history of trauma to the testicles, mumps with inflammation of the testicles, impotence, ejaculatory problems, diabetes or other illnesses. In particular we are interested in any exposure to toxic substances such as pesticides and we can also benefit from discussing the noxious effects of tobacco and other drugs on fertility.
In more than a third of couples, an anomaly will be found in the semen analysis. It is the reason why the semen analysis will always be ordered at the start of investigations, even if the man has already fathered a pregnancy with his current partner or a previous partner. We will ask you to abstain from ejaculating for two to three days prior to the test. The semen must be collected into a sterile container at the clinic or at home as long as the sample can be brought to the clinic rapidly (within one hour). Abnormalities in terms of count, mobility and / or morphology of the sperm may be discovered. If the semen analysis is abnormal it will always be repeated a second time approximately one month later. If the result is still abnormal, we will refer you to see an urologist who specialises in male fertility to complete your questionnaire and examination. If it is indicated a blood sample may be ordered. The urologist will look for any problem especially any which may be treated in order to improve the semen analysis. A varicocele may be identified during examination of the testicles, almost always on the left side. When the varicocele is sufficiently large on examination, surgery to cure the varicocele will be offered and may improve the semen analysis and the chance of conception. Unfortunately a treatable cause will not be found in a minority of men. According to the severity of the problem, we can offer you intrauterine inseminations with sperm washing, or in vitro fertilisation with microinjection of the sperm.
For many years, the infertility work-up included the post coital test. This test has now been abandoned because it is not reliable at evaluating the fertilising potential of sperm.
Tubal Factor Infertility
Patent tubes are essential for fertilisation to occur naturally. It is halfway along the tube that the egg and the sperm meet. The fertilised egg, i.e. the embryo will arrive in the uterus approximately 5 days after fertilisation and will implant on the sixth day. Your tubes can have been damaged by a previous or recent infection caused by a sexually transmitted disease such as Chlamydia or by an infection from elsewhere. (e.g. appendicitis with peritonitis). Moderate to severe endometriosis may also cumulatively affect the tubes. The hysterosalpingograph is the test which allows us to check the permeability of your tubes. This technique involves the injection of a contrast iodine product and several x-rays. This examination will be done between day 5 and day 10 after the start of your menstrual cycle. Menstrual type cramps may be experienced during and up to 24 to 48 hours after the procedure. An anti-inflammatory such as Naprosyn or ibuprofen will help to reduce the cramps. One or both tubes may be blocked and/or dilated. A laparoscopy may then be necessary to confirm the blockage and evaluate the extent of the disease. The laparoscopy will be diagnostic and may also be therapeutic. During the procedure, your physician may attempt to unblock the tubes, remove any adhesions, catheterise any endometriosis; basically, he will try to do everything possible to improve your chances of pregnancy. Nowadays all fertility surgery can be performed by laparoscopy with fewer complications and less time for recovery than traditional surgical methods.
Ovulatory factors
Anovulation explains the problems in about 15% of couples. If you have regular menstrual cycles, it is unlikely that you have a problem with ovulation. However, to be sure of ovulation, we will ask you to make a graph of your basal temperature each day for a month and we will do a blood test for progesterone during the luteal phase of your cycle, just before your period. If your periods are very irregular (between 30 and 60 days or just a few periods per year) it is obvious that there is a problem. You ovulate occasionally perhaps, but since the ovulations are rare, the chances of falling pregnant are also rare! Prolactin and TSH (the hormone that stimulates the thyroid gland) will be evaluated because some endocrine disorders can cause problems with ovulation. The level of FSH will allow us to eliminate insufficient ovarian response (premature menopause). If you notice that you are hirsute and that you gain weight easily, you probably have polycystic ovarian syndrome. These women are classically anovulatory, hirsute, and often obese. The ovaries have lots of small follicles (cysts) on ultrasound. Resistance to insulin is often increased in these women who are also at risk for diabetes and hypercholesterolemia. If you have a problem with ovulation, your physician will suggest inducing ovulation with the use of ovulation agents such as clomiphene citrate. If your level of insulin on an empty stomach is elevated, a glucophage will be prescribed which could help you to ovulate.
Clomiphene citrate has been used in the treatment of anovulation since 1962. It acts as a selective estrogen. It increases FSH to stimulate the ovaries. In anovulatory women, we obtain an ovulation rate of between 60 and 85% with a pregnancy rate of 30 to 40%. If we are unable to induce ovulation with clomiphene citrate, we will use small doses of gonadotrophins.
Unexplained Infertility
In about 10% of couples, investigations will not turn up any problem. The couple may choose to continue to try for a pregnancy without help for several more months or years. If the woman is less than 30 years old and you have been trying for less than 3 years there is a 60% chance that you will conceive naturally during the next three years. However, the majority of couples who consult with a fertility clinic are in a hurry and do not want to wait. We can offer superovulation by a method that suits the choice of the couple, the number of year's infertility and the age of the woman. The more years of infertility and / or the older the woman, the more quickly it is indicated to start superovulation.
We will start by using clomiphene citrate, a medication which is taken orally from day 3 to day 7 of your cycle. Clomiphene citrate will increase 'boost' ovulation. The risk of twins will be increased to 5% as compared to 1% in spontaneous pregnancies. The side effects are usually little and may include hot flashes, head ache and irritability. Since the majority of pregnancies occur within three months of proceeding with a treatment, if you have not conceived after three months your physician will suggest modifying the treatment. The next step would be adding intra-uterine inseminations to the clomiphene citrate treatment for another three months.
If there is still no pregnancy, generally a laparoscopy will be suggested, if it has not already been done. This surgery allows us to visualise the tubes and to ensure that they are normal. Endometriosis will be looked for and if seen can be catheterised. Any abnormalities likely to harm fertility will be corrected, if possible.
Following this, stronger superovulatory medication, gonadotrophins, will be used. This will consist of daily injections, for about 12 days, into the muscle or skin, which stimulate the ovaries to produce more eggs. These injections are usually given by the partner. We will proceed with an intrauterine insemination once ovulation is obtained. The side effects are generally associated with the discomfort of the injection. After three months of this treatment, if there is still no pregnancy, in vitro fertilisation will be the next option.
We obtain a monthly pregnancy rate of 5.6% with clomiphene citrate which increases to 8.3% by adding intrauterine inseminations. The pregnancy rate obtained with gonadotrophins and intrauterine inseminations is 17.1% per cycle and 30% or more with in vitro fertilisation. Figure 1. It must not be forgotten to compare the results with the fertility rate of a normally fertile couple which is 20%.
Age
Men remain fertile for a long time. The testicles produce new sperm constantly. This is not the same for a woman. The quantity of eggs in the ovaries decreases consistently until menopause. Menopause occurs usually around 50 years of age when the reserve of eggs is exhausted. A third of women between 35 and 40 years old will have a problem of fertility and more than half of women over 40. Over the last few years, the number of to fertility clinics has increased. As more and more women wait until the end of their 30's to start their families because of their career or simply because the 'right' man has not yet appeared. The risk of having been exposed to a pelvic infection or having developed endometriosis increases with age. Additionally, the ovarian reserve starts to significantly decrease after 35 years of age in most women. The risk of a miscarriage also increases with age. Although the risk is 10 to 15% in women under the age of 30, it increases to 40% in women over 40 years old. For sure, you must not try for a child if it is not the right moment but if you want to have children and you are approaching your 40's, it would be better not to wait too long.
Endometriosis
Endometriosis is diagnosed in 30 to 40% of women who present at a fertility clinic. It is a matter of the small endometrial glands (the internal lining of the uterus) passing into the tubes during menstruation and then implanting in the pelvic cavity on the ovaries, in front of and behind the uterus, and sometimes on the bladder or intestine. It is a disease which is sometimes extremely annoying and which has several facets. Endometriosis may cause period pain, pain during sexual relations and also may be associated with infertility. Certain women with severe endometriosis have no pain and no difficulty becoming pregnant which makes this disease a true mystery. Studies have shown that when we find endometriosis during a laparoscopy and we treat it, we increase the chance of pregnancy.
Tubal Anastomosis
You have had a tubal ligation in the past. Life has changed and now you regret it. You have a new partner or perhaps the same partner but you would like to have another child. You physician will evaluate you request carefully and see which technique was used to perform you ligation originally. It is not always possible to reverse the procedure and even if you are offered surgery, the chances of pregnancy are in the region of 70%. Traditionally, tubal anastomosis would be performed by laparotomy, i.e. an incision in the bikini area and several weeks convalescence. A tubal anastomosis technique by laparoscopy has been developed in recent years with equivalent chances of success. It is performed as day surgery and the period of convalescence is only a matter of days.
In Vitro Fertilisation
The last step in the treatment of infertility is often in vitro fertilisation. There are certain situations where in vitro fertilisation will be the only option. For example, in a couple where the woman has had repeated ectopic pregnancies and as a result she has lost her tubes. Or in a couple where the sperm anomalies are significantly elevated and the use of donor sperm is not an option. Or if you are 41 years old and do not want to waste any time. The principle inconveniences of in vitro fertilisation are the stress, the clinic visits which can be numerous, and the costs. The medication is sometimes reimbursed partially or completely by insurance companies. The cost of the in vitro fertilisation is never reimbursed except for a tax return of 30% by the government. The costs of in vitro fertilisation are higher but the chances of success are a lot greater than the other treatments and are between 30 to 50% in a woman of 35 years old or less. The age of the woman is the most important factor and the pregnancy rate is not more than 15 to 20% in women between 40 and 42 years old.
After a total evaluation and blood profile, if you are considered a good candidate for in vitro fertilisation, you will start your medication at the time of your period. The first medication is given subcutaneously and allows us to put your ovaries into a state of quiescence so that we can control your cycle and prevent a spontaneous ovulation. After suppression, the gonadotrophins are started in order to stimulate the ovaries to produce several eggs. The eggs will be collected under ultrasound through the vagina then inseminated in the laboratory with your partner's sperm. Two or three days, and sometimes five or six days (embryo at the blastocyst stage) later, two or three embryos will be placed in your uterus. Progesterone tablets will be put in the vagina every day to help the embryos to implant. The pregnancy test is performed two weeks after the egg collection. In vitro fertilisation has existed for more than 20 years. With this technique many couples have been able to conceive when otherwise adoption would have been their only option. For more than a dozen years, the microinjection of sperm directly into an egg has allowed azoospermic (absence of sperm in the ejaculate) men to conceive also. In some cases the sperm can be obtained directly from the testicles and injected into the eggs. Egg donation allows women with premature ovarian failure or who have a poor response to the stimulation of in vitro fertilisation to carry their own pregnancy. The eggs of an anonymous donor are fertilised with the partner's sperm and the then the embryos are replaced into the uterus of the female patient.
Conclusion
Do you have a parental project? Have you wanted to have a child for one or more years? Your situation is special or you would like a second opinion? We are here to help you. We have spoken more and more openly about infertility for several years. Couples are better informed and information is distributed more easily. Consultations at infertility clinics are increasing. The investigations have been simplified over the years and are a lot easier for the couple. At the fertility clinic we will attempt to answer your concerns and questions as well as possible and respect your choices. Certain couples do not seek consultation that may have a problem that can be corrected without the need for treatment and medication. Others will never go as far as in vitro fertilisation by choice or due to the costs. Others we consult with in parallel with their plans for adoption. During the last few years, 65% of couples who have consulted with us have had a pregnancy before taking the step of in vitro fertilisation. We will do everything that we can to help you to realise your dream……..a child.
References
1. Speroff L, Glass RH, Kase NG. Clinical Gynecologic Endocrinology
and infertility. Sixth Edition. Lippincott Williams & Wikins. 1999.
2. Chandra A, Stephen EH. Impaired fecondity in the United States :
1982-1995. Fam Plann Perspect 1998; 30 :34-42.
3. Collins JA et al. The prognostic for live birth among untreated infertile
couples. Fertil Steril 1995; 64 :22-8.
4. Eimers JM et al. The prediction of the chance to conceive in subfertile
couples. Fertil Steril 1994; 61 :44-52.
5. Kousta E, White DM and Franks S. Modern use of clomifene citrate
in induction of ovulation. Human Reprod Update 1997; 3 :359-365.
6. Marcoux S, Maheux R, Bérubé S, et the Canadian Collaborative
Group on Endometriosis Laparoscopic surgery in infertile women with
minimal or mild endometriosis. N Engl J Med 1997; 337 :217-222.
7. Bissonnette F, Lapensée L, Bouzayen R. Outpatient laparoscopic
tubal anastomosis and subsequent fertility. Fertil Steril 1999; 72 :549-552.
8. Cuzick DS et al. Efficacity of superovulation and intrauterine insemination
in the treatment of infertility. N Engl J Med 1999; 340 :177-183
9. Bissonnette F, Lapensée L. L’investigation et le traitement
de l’infertilité, où en sommes-nous? Le Clinicien
Février 2000
10. Bissonnette F, Lapensée L. La reproduction médicalement
assistée, où en sommes-nous? Le Clinicien Mars 2000
