Ovulation problems
An ultrasound scan of the pelvis together with blood and urine hormone assays can confirm ovulation and evaluate any problems. The ultrasound scan highlights the ovarian follicles, which are bubbles of liquid containing oocytes that increase in size when the latter reach the maturation phase.
Follicle rupture, which leads to the release of the oocyte (= ovulation) is triggered by a hormone, LH, detected in large quantities in the preceding 24-hour urine.
Simple tests available from pharmacies can detect this hormone peak. Ovulation is confirmed by a progesterone blood assay one week after ovulation or by the disappearance (collapse) of the dominant follicle on ultrasound scanning after follicular rupture.
Infertility of fallopian tube origin
Hysterosalpinography (HSG) is the examination most frequently used to evaluate a tube-related problem. This is a radiological examination in which a liquid (contrast medium) is injected into the uterus and fallopian tubes from the Cervix uteri. The passage of the liquid is monitored on a screen.
Approximately 4 to 5 X-rays are taken during the examination. The irradiation dose is very low. The liquid fills the uterine cavity, outlining the contours, and then continues to the end of the fallopian tubes where it freely flows off if the tubes are healthy. If the liquid does not pass through the fallopian tubes, does not fill them completely or fails to run off at the end of the tube, the latter are probably damaged in some way.
Diagnosis will then be based on an examination that directly displays the fallopian tubes: laparoscopy. This is a minor surgical procedure carried out under a general anaesthetic. An optical lens tube (laparoscope) is introduced through the navel via a small incision (about 1 cm).
The laparoscope is connected to a camera and a television monitor to give an excellent view of the internal female organs (uterus, ovaries and fallopian tubes). The injection of a blue dye into the fallopian tubes from the Cervix uteri confirms whether or not the tubes are permeable. Laparoscopy can also detect other pelvic diseases and is used for the surgical treatment of any lesions.
Clomifene
Clomifene acts by blocking oestrogen receptors in the hypothalamus, thus making it "believe" that the circulating oestrogen level is too low. The hypothalamus then gives the Pituitary gland the order to secrete more FSH and LH. The increase in FSH stimulates the growth of the ovarian follicle, which, in turn, releases large quantities of oestrogens. About one week after the last tablet has been taken, elevated oestrogen levels detected by the hypothalamus trigger an LH peak, which, in turn, triggers ovulation.
All of the ovulation inducers increase the risk of multiple pregnancies. The risk of having twins is approximately 10% with clomifene, and the risk of having triplets or more than three children is less than 1%. Other adverse events observed include hot flushes, mood swings and, very occasionally, headaches and impaired vision.
Clomifene may have a negative effect on the quality of the cervical mucus and the thickness of the uterine mucosa. The chances of pregnancy are reduced in such cases. This explains why clomifene is not usually indicated in women who ovulate normally and in certain ovulation-related disorders during which this effect is particularly marked.
L’hMG et la FSH
Preparations containing only FSH have been available for a few years, now. These products used to be of urinary origin, the LH of which had been removed. Current preparations, however, contain purified FSH of urinary origin (u-FSH, Fostimon®) or recombinant FSH (r-FSH), i.e. pure FSH, the exact formula of which has been synthesised in the laboratory (Gonal-F®, Puregon®). Like hMG, FSH is administered in the form of injections and directly stimulates follicle growth in the ovary. FSH can be used in all women producing sufficient endogenous levels of LH and in some ovulation disorders in which abnormally high levels of LH are observed in the presence of a low or normal FSH.
The administration of hMG or FSH involves daily injections under strict medical monitoring. Treatment lasts approximately 7 to 12 days, sometimes longer if the ovarian response is slow. Treatment response is evaluated by ultrasound scans and blood tests to measure oestrogen levels (on average, 2 to 3 times per cycle). When the follicles reach maturity, ovulation is triggered by an injection of hCG.
hMG and FSH are more potent and more difficult to manage ovulation inducers than comifene. Despite intensive monitoring, the risk of multifollicular development and, therefore, multiple pregnancies, is of the order of 25% per cycle. Twins are mostly conceived but triplets or quadruplets, etc. are also feasible. This is why, if too many follicles are stimulated or if oestrogen levels are too high, ovulation should not be triggered as a precautionary measure, and treatment should be interrupted.
Other potential side effects associated with hMG and FSH include breast tension, mood swings, water retention, abdominal pain, weight gain and a skin reaction at the injection site. Ovarian hyperstimulation syndrome is the most serious adverse event. Over-stimulated ovaries are swollen and painful. In severe cases, liquid accumulates in the stomach and chest. Hospital admission is warranted in approximately 1% of cases. Ovarian hyperstimulation syndrome resolves spontaneously over time. It can be avoided in most cases provided that ovulation is not triggered.
IVF : Ovarian stimulation
The hormone preparations used for stimulation purposes are hypophyseal gonadotrophines (hMG or FSH), as for inducing ovulation, but higher doses are administered. The development of several follicles at the same time is associated with a rapid rise in oestrogen levels – the main product of the ovarian follicle. These high levels may trigger ovulation prematurely.
To avoid this complication, ovarian stimulation is preceded by injections that allow hypophyseal gonadotropin reserves to be emptied. The natural hormone cycle thus no longer interferes with treatment. The substance that enables this result to be achieved is known as a GnRH agonist. The product used most frequently is Decapeptyl®. This is a highly specific substance, the only effect of which is the temporary suppression of the growth of ovarian follicles. Decapeptyl® generates a hormone climate similar to that of the menopause and can trigger menopausal symptoms (hot flushes and headaches). The latter are of short duration and disappear as soon as the follicles regrow and secrete oestrogens in response to gonadotropin injections.
DIn the so-called "long" protocol, which is most commonly used, Decapeptyl® is administered for around 10 days prior to the onset of stimulation. This period can be reduced to 7 days by the prior administration of a contraceptive pill, which slows down hypophyseal activity. In the so-called “short” protocol, the GnRH agonist is administered only for one or two days prior to the onset of stimulation. Its effect on emptying hypophyseal reserves of FSH and LH is used to potentiate the stimulating effect of gonadotropins that can be injected into the ovary.
The choice of the stimulation protocol and the injectable hormone preparation is adapted for each patient according to age, hormone assays and the outcome of any previous therapy.
Ovarian stimulation takes 10 to 14 days on average. During this period, Decapeptyl® and the gonadotropins are administered daily by subcutaneous injection. The doctor regularly evaluates the treatment response by examining the ovaries (ultrasound scan) and assaying oestrogen levels (blood tests). Between 8 and 12 follicles would ideally develop but some women have more than 30 and others less than 5.
