By the fifth month of its intrauterine life a fetus contains 7 million oocytes in its ovaries. Of these oocytes, half will die until the fetus is born, and by adolescence only 200,000-500,000 oocytes will have survived. During her reproductive life, a woman will need 400-500 oocytes.
The time oocytes remain in the ovary is crucial. The precursor germ cells and primordial oocytes are particularly sensitive to environmental factors, such as radiation and medications. The oocytes to be released during a woman’s last ovulations will have spent more than 40 years in the ovary, and during all this time they are subjected to the adverse effects of the environment. This is the reason why older women run an increased risk of giving birth to a child with genetic disorders.
If a woman’s menstrual cycle (period) is heavier than normal and slightly delayed, an incipient pregnancy may end in miscarriage. In terms of prognosis, it is very important that conception is confirmed. For this reason, a hCG (human Chorionic Gonadotropin) test is recommended. If the result of the test is positive but gestation fails to progress, we then talk about a biochemical pregnancy.
On average, a normal fertile couple aged 25 years, who engage into frequent unprotected sexual intercourse, runs a 25% chance to conceive every month. Most of these couples (80-85%) will be able to conceive within a year, while 90% of fertile couples will have achieved a pregnancy within three years. The period that a couple tries to conceive is very important for study designs, as it helps specialists identify the medication or infertility treatment with superior success rates. Typically, studies accept couples who are trying for a pregnancy at least three years.
Yes, men also go through the same process, but the decline of male fertility by age is slower. A recent investigation conducted at the University of California, Berkeley, USA, studied the sperm of 100 healthy men aged 22-80 years. The investigators found that sperm count and motility are lowered by 0.7% on an annual basis. In practice, they estimated that 25% of men will suffer sperm abnormalities at the age of 22. These rates go up to 40% at the age of 30, 60% at the age of 40 and 85% at the age of 60. Thus, despite the news that an actor became a father at the age of 70, the likelihood of this happening is rather small.
To a great extent, this depends on the age of both partners, as well as on the infertility causes. In general, a good Clinic should present steady success rates. The anticipated successful pregnancy rates are 50-60% in patients monitored for a period of 2 years.
The ‘Anti-Müllerian Hormone’ (AMH) is produced in small ovarian follicles and it is very useful in determining the ovarian reserve in women. It neither indicates the number of good oocytes in the ovary nor does it predict miscarriages. Overweight women may have up to 30% lower AMH levels compared to normal levels for their age. The greatest advantage of AMH is that it can be measured at any day of the menstrual cycle.
According to the American Society of Reproductive Medicine, endometriosis is staged into 4 levels: I-minimal, II-mild, III-moderate, and IV-severe. In the case of severe endometriosis, all specialists agree that damaged Fallopian tubes, adhesions and generally anatomical abnormalities can cause infertility.
The relation of mild forms of endometriosis with infertility, however is not clear and compares to the ‘Chicken-or-the-Egg’ dilemma; half of the specialists advocate that a woman cannot get pregnant due to endometriosis, while the rest claim that she developed endometriosis because she did not get pregnant at a young age.
Fibromyomas or fibroids are non-cancerous tumors that arise from the uterine muscle tissue. They are common in older women, and are found in one in three women aged 40 or more. A lot of women with fibroids conceive spontaneously, carry the pregnancy and deliver without facing any problems at all.
However, fibroids may cause infertility, when their size is big and displace the tubes and the ovaries, when they distort the uterine cavity, and when they obstruct the Fallopian tube by growing close to the area where they enter the uterus.
Pure male factor is the cause of 30% of infertility cases, but is also affecting an extra 20% of cases, when combined with female factors. Despite that only recently, the field of andrology has witnessed some serious development.
A number of men avoid having their sperm tested because they wrongly link masculinity to impotence. in fact, they are not connected at all. Most men with erectile dysfunctions, which impedes a normal sexual life, have strong sperm. On the other hand, men whose sperm is weak, do not exhibit sexual dysfunctions. On many occasions, this psychological vicious circle ends up affecting a couple’s quality of life, or even resulting in complete sexual abstinence.
The sperm duct is surrounded by a venous network. When the veins in the scrotum dilate, the blood slowly runs through them, causing the testicle’s temperature to rise. This is believed to be the primary way varicocele affects spermatogenesis. Nonetheless, the explanation is not widely accepted by andrologists. A lot of men suffering from varicocele are fertile, while a great number of infertile men do not exhibit varicocele.
The term actually means that the specialists were not able to identify the cause of the problem. Occasionally, the term is referred to as ‘idiopathic’, in order to sound a bit more scientific. The lower the rates of unexplained infertility in a Clinic, the more carefully fertility specialists do their work. A good Clinic would demonstrate no more than 5%, 10% at the most, of unexplained infertility cases.
This is particularly significant for the following reasons:
- If the cause of infertility is unknown, treatments are usually empirical. Success is simply a matter of luck.
- Usually, specialists recommend costly treatments, such as IVF, hoping that they will be effective. However, not only they fail some times, but they do delay the appropriate diagnosis.
- Upon the diagnosis of unexplained infertility, a couple may suffer an even greater psychological burden.
- Certain types of gynecological cancers are more common in women with unexplained infertility. Therefore these women need careful monitoring, even after the end of the treatment and possibly for a lifetime.
IVF can be useful in the following cases:
- When the Fallopian tubes have suffered severe damage that cannot be reversed with tuboplasty or when tuboplasty has failed. In this case, the Fallopian tubes are bypassed with IVF.
- In cases of anovulation, e.g. in women with polycystic ovaries.
- In women with endometriosis.
- In healthy women, whose husband/partner has severe sperm problems.
- In couples suffering from unexplained infertility.
- In couples harboring a genetic defect and preimplantation genetic diagnosis and the subsequent placement of healthy fetuses into the uterus is planned.
All drugs used to stimulate the ovaries are extremely safe; they are being used for decades, and no reports of adverse effects are found in the international literature.
In particular, there are no reports of increased frequency of ovarian cancer.
With regard to breast cancer, thorough research has shown that childless women demonstrate high breast cancer rates compared to the general population, regardless of undergoing IVF treatment or not. Women that have been subjected to IVF treatment and have children, exhibit the same rates as the general population.
Some women fear that ovarian stimulation may cause premature menopause, but this is not the case.
The most serious complication is the ovarian hyper stimulation syndrome. In this case the ovaries are very sensitive to the medication. Today we use many interventions to minimize the chances of this syndrome occurring.
It is true that more blastocysts than 2- to 3-day-old fetuses will be implanted. However, not all lab developing embryos advance to the blastocyst stage; therefore, there is a risk that some women may have no embryos to transfer. Taking also into consideration those women who will not undergo embryo transfer, the overall pregnancy rates are similar.
Blastocyst transfer has a place when we have many embryos and we want to choose one or two for transfer.
A couple can try as many times as they want, since there is no IVF treatment cycles limit. But, given that every attempt is accompanied by physical, financial and psychological burden, it is recommended that every new attempt is made after three months of rest. It has been found that when attempts are made on a monthly basis, the ovaries require higher medication dosages only to produce less oocytes.
The oocyte shell is a relatively thick and resistant membrane, called transparent zone (zona pellucida). In cases of male infertility, the likelihood of a spermatozoon penetrating the transparent zone and fertilizing the oocyte is rather small. For this reason, micromanipulators have been invented to allow the performance of complex microsurgery on the oocyte, under magnification of 100-600 times.
The oocyte is held by a micropipette and a needle is used to aspirate the sperm. The needle is inserted into the oocyte and releases the sperm into the egg. The diameter of these special pipettes is 10 times smaller than the diameter of a piece of hair (diameters range from 5μm to 150μm).
The pediatric monitoring of children born after ICSI treatment is quite encouraging. Genetic defects rates are similar to those of IVF treatment. Yet, the results of each newer technique should be recorded and monitored in the long term. There are certain genetic mutations in the male Y chromosome that could be transferred to the fetus. If a girl is born, no issue arises. But, if a boy is born, it could harbor the same infertility problem with its father.
‘Egg donation’ refers to the use of one woman’s eggs (egg donor) to help another woman (egg recipient) conceive.
This method can be applied either because a woman does not produce oocytes (eggs) or because her oocytes harbor a genetic condition.
Women suffering from ovarian failure due to Turner’s syndrome or ovarian dysgenesis, as well as women whose ovaries were damaged by severe endometriosis, radiation, chemotherapy or surgery, are the best candidates for egg donation.
Premature menopause, auto-immune diseases and multiple unsuccessful IVF attempts (failure to fertilize the oocytes or failure of fetal development) also constitute indications for egg donation. Women harboring a inherited x-linked genetic disorder, such as Huntington’s disease or Duchenne muscular dystrophy, usually opt for having a healthy child using another woman’s oocyte.
This technique was first applied by our team at the Hammersmith Hospital in London, back in 1990. It aims at diagnosing certain diseases in the embryo, before it is implanted into the uterus. The couple undergoes standard IVF treatment, even when no fertility problem exists. The developed embryos are screened for the genetic disease of their parents. Only healthy embryos or carriers of a disease are transferred into the uterus. Prenatal testing and confirmation of the diagnosis is advisable in these cases.
An exceptionally optimistic newer technique, which is applied over the last few years, is ‘Oocyte Cryopreservation’ (oocytes are frozen before they are fertilized). It concerns single women diagnosed with cancer, whose oocytes cannot be fertilized because they do not have a husband/partner. The first ever successful human gestation with cryopreserved oocytes was reported in 1997; since then, other gestations have also been reported. The oocyte is the largest human cell. During its freezing and thawing stages, ice crystals are formed and destroy the oocyte.
This newer technique of oocyte vitrification is extremely fast and can successfully address the aforementioned problem.
Until now, literature cites 8 childbirths from cryopreserved oocytes in women with cancer.
Many more women are now opting for social freezing because of delaying childbearing due to social or economic reasons.
Overall, infertile women run the same risk of developing cancer as fertile women. The exception to the rule is endometrial cancer, which demonstrates increased frequency in women with anovulation and unexplained infertility. No increased frequency of cancer has been linked either to fertility medications or IVF techniques.