This description is not intended to be a complete guide to every form of available therapy. Should any doubt exist, you should ask your doctor for advice.
The object of treatment is the release of a fertile egg(s)
1.1. i Weight:
a) Obesity - not only is being overweight a possible cause of failure of ovulation, and possibly other causes of infertility, but also has detrimental effects on pregnancy, health and increases the risks of surgery. Controlled weight loss can aid ovulation. Certain patients with obesity may have PCOS. Patients with both obesity and who are underweight will have lower pregnancy rates with ART.
While body weight is important there is a better method of correlating weight and disease and this is the BMI. BMI stands for "Body Mass Index," a ratio between Weight and Height. It is a mathematical formula that correlates with body fat.
BMI Underweight :
|18.5 - 24.9
|25.0 - 29.9
|30.0 and Above
Fat predominantly distributed around the waist is also a risk factor for
health complications such as cardiovascular disease and type II diabetes. Fat
predominantly deposited around the hips and buttocks doesn't have this same
It is worthwhile to try and get your BMI into the healthy range!
b) Underweight - if your weight falls below a certain level it too can interfere with ovulation and again one must discuss this with your doctor, as controlled weight gain can aid ovulation. Being underweight often occurs in people who exercise excessively or may have eating disorders. Medical advice in these circumstances is essential.
1.1. ii Drugs:
Patients often feel that one form of medication is stronger than another. This is not true. For each ovulation problem there is usually a specific form of treatment. Remember that once ovulation occurs, it only continues with the repeated monthly use of the medication. There is rarely any permanent cure. Also, once ovulation occurs, the monthly chance of conception is provided, so the patient should not necessarily expect pregnancy to occur during the first month (even though these drugs are called "fertility drugs", in reality they are ovulatory drugs).
There are basically two broad groups of drugs available, those acting directly on the pituitary gland and ovary, and those acting indirectly:
a) Clomiphene Citrate (Serophene, Clomid)
This is the most commonly used agent for inducing ovulation and is taken in tablet form. Methods of use vary, but the drug is usually taken early in the cycle, commonly commencing on Day 5. The correct dosage needs to be established, overstimulation prevented by ultrasound and confirmation of ovulation should be checked during each cycle. In patients who do not ovulate, the consequences of ovulation viz. certain hormonal effects on breasts, fluid retention and menstruation may not occur. Furthermore, it is possible that despite the use of clomiphene citrate no ovulation will occur on certain treatment cycles. There is no specific evidence to show that the prolonged, controlled use of clomiphene citrate has any untoward effects on the female, however use longer than 12 months is not recommended. In addition there is no definitive evidence to show that its use has any adverse effects on the child born as a result of its use.
b) Human Menopausal Gonadotropin (HMG) (Humegon, Pergonal, Metrodin)
This form of treatment is given by injection and its use must be carefully monitored by either blood tests (to check oestrogen levels) or ultrasound or both. Some of these medications are no longer available. These products are derived from the urine of menopausal women as suggested by the name. The drug usually has equal amounts of FSH and LH activity, measured in iu (International Units) It tends to be used for more severe types of ovulatory problems and often for Assisted Reproduction where multiple oocytes are required. The world requirements for this drug have outstripped its supply and this led to the production of newer products using recombinant gene technology.
c) Recombinant FSH and LH (rFSH, rLH) (Puregon, Gonal F)
Recombinant FSH and LH has replaced HMG. The technology involves genetic modification of cells growing in the laboratory to produce very pure forms of the naturally occurring hormones FSH and LH. No doubt other hormones will be produced in a similar fashion in the future.
d) Human Chorionic Gonadotropin (HCG) (Pregnyl, Profasi)
This drug is given by injection, and is used to trigger ovulation. It has an action similar to LH and is used to imitate the LH surge. It is usually given in conjunction with HMG and occasionally with clomiphene citrate. Once triggered, ovulation tends to occur approximately 36 hours after the use of HCG.
e) Chorionic Gonadotropin Alfa (Ovidrel)
This is the recombinant form of HCG and can be used in its place.
By virtue of their action, both clomiphene citrate, HMG and recombinant agents are associated with increased risk of multiple pregnancy. However, when used and monitored correctly, the likelihood of multiple pregnancies is reduced.
a) Bromocriptine, Cabergoline
Elevated levels of prolactin (see p.29) either prevent or reduce the quality of ovulation. Bromergocriptine or Cabergoline is given to return the prolactin levels to normal. Stopping treatment even for a few days allows prolactin levels to increase, and the medication should therefore be taken continuously unless otherwise advised by the doctor.
Dangerous side effects of these agents are extremely rare and there is no specific evidence to show that they lead to birth defects in children. However, bromocriptine may have some initial unpleasant side effects on some patients, e.g. headaches, dizziness associated with low blood pressure, "stuffy" nose, or nausea. These side effects are overcome by gradual increase to the prescribed dose, and taking of the medication in the middle of meals. Cabergoline tends to have far fewer side effects and is replacing bromocriptine as the drug of choice especially as it is taken once a week.
Thyroxine: used to treat an under-active thyroid gland.
used to suppress abnormal male hormone production
and in the past to suppress male antisperm antibodies.
Gonadotropin Releasing Hormone (GnRH) Agonists
(Luprorelin nafarelin, goserelin): used to suppress the pituitary gland in special patients requiring HMG, HCG therapy eg IVF programmes. This type of suppression is referred to as down regulation. The normal pituitary axis and ovary functions to ripen and release one oocyte per cycle. Assisted reproduction requires the ripening of multiple oocytes for collection, and so the ovary has to be hyperstimulated (controlled deliberate overstimulation). If the pituitary gland is active it will interfere with this deliberate overstimulation and so it has to be down regulated (switched off).
Gonadotropin Releasing Hormone (GnRH) Antagonists
(Cetrorelix and Ganirelix)
These newer agents are becoming universally available. They also lead to down regulation of the pituitary gland and may be more efficient than the agonists.
Metformin hydrochloride (Glucophage)
This agent initially used to treat non insulin dependent diabetes (adult onset diabetes) thought to be due to insulin resistance is sometimes prescribed for patients with Polycystic Ovarian Syndrome who have obesity and elevated blood androgen levels.
In patients with polycystic ovarian syndrome, laparoscopic ovarian drilling has been shown to induce ovulation. Ovarian Drilling is performed by making 4 or 5 small holes in each ovary with a diathermy probe. Obviously this is a destructive procedure and should only be performed by a suitably trained fertility specialists once you complete infertility investigation. Excessive diathermy can lead to ovarian damage.
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This is a condition in which tissue resembling the normal lining of the uterus (endometrium) is found outside the cavity of the uterus. It may occur on the ovaries, tubes, outside of the uterus or anywhere in the pelvic cavity, rarely elsewhere. Its presence can lead to local inflammation, scarring and pain.
The incidence of endometriosis varies but is thought to affect ± 21% of infertile women. It is best diagnosed with laparoscopy but ultrasound does help in diagnosing ovarian endometriotic cysts (endometrioma).
When present in minor amounts, just a few spots and without causing any other complaints, it can lead to infertility and its removal usually laparoscopically leads to an improved chance of pregnancy in about 35% of cases. This result is further increased if surgery is followed by induction of ovulation and intra uterine insemination. In other words removal of endometriosis creates a "window of opportunity" for fertility and this is magnified by including other fertility treatment options.
When present in moderate or severe forms it may add a secondary mechanical cause of infertility, affecting the tubes alibility to collect eggs due to scarring and adhesions. Although a poorly understood condition, it is associated with an increased risk of infertility. Drugs, surgery or assisted reproductive techniques may be used in treatment, and your doctor will decide what form of therapy is appropriate. At present there is no cure, but control is possible.
Basically drugs are used to treat the symptoms of endometriosis, such as pelvic pain, progressive dysmenorrhoea and pain on intercourse, but do not increase the chances of pregnancy whereas surgery increases the pregnancy rate as well as treating symptoms. Surgery can also lead to healing by scar tissue which itself can aggravate infertility, so this type of treatment should be carefully discussed with your infertility expert. Once a woman is pregnant endometriosis has no effect on the pregnancy. Endometriosis does not affect IVF outcome. Pregnancy on the other hand leads to an improvement or cure of the endometriosis, a wonderful bonus for the sufferer. The aim of therapy is to reduce the amount or effect of endometriosis and so maximise the chance of conceiving.
Drugs used to treat endometriosis include:
Progesterone: Usually as medroxyprogesterone acetate or in the form of the oral contraceptive pill
*These two drugs are derived from synthetic male hormones and may have mild side effects as a result. These side effects may include development of oily skin or hair, some acne, or weight gain. These effects are usually mild and reversible. Treatment using these two drugs often lasts up to six months. While on treatment your menstruation will diminish and usually stop altogether. This is quite normal. Provided the drugs are taken correctly, conception cannot take place during this form of treatment as it stops all ovarian activity. These drugs are usually used to control symptoms but do not appear to improve fertility.
GnRH Agonists ( as nasal spray, short or long acting injectable (depot) forms )
This type of medication is prescribed to minimise the effects and amount of endometriosis prior to surgery. Occasionally oestrogen and progesterone must be added in small amounts to prevent osteoporosis (weakness and brittleness of bones) and this is referred to as "add back therapy".
These drugs are currently undergoing trials prior to release and we await information regarding their potential role in the treatment of endometriosis.
Letrozole is one example. Its action is to block oestrogen synthesis on the basis that the development of endometriosis is oestrogen dependent. Research with this type of drug is ongoing.
Surgery is also used to treat endometriosis and has a number of objectives:
- Reducing the amount of endometriosis and improving the chance of fertility.
- Control of pain as a result of the scarring and inflammation caused by endometriosis.
- Correction of mechanical problems which can effect the function of the Fallopian tubes.
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(i)An alkaline vaginal douche prior to intercourse will correct acid problems affecting the cervical mucus. Far less commonly, an acid douche may be used for excessively alkaline mucus. These are rarely prescribed, as most cervical problems are by-passed by intrauterine-insemination of prepared sperm.
If you suffer from stomach acidity or stomach or duodenal ulcers, this has nothing to do with your cervix. Thus diet does not affect the state of your cervical mucus.
(ii) Insemination of prepared sperm into the uterus (intrauterine insemination / IUI) will by-pass hostile mucus caused by local factors or sperm antibodies.
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Although developmental abnormalities of the uterus do not usually prevent conception, they may have effects later in a pregnancy and may require correction prior to attempting conception. This subject is complicated and needs to be discussed with your infertility specialist.
Similarly, if smooth muscle tumours of the uterus, i.e. fibroids (fibromyomata), are close to or project into the uterine cavity they must be surgically removed (myomectomy). Instead of open abdominal surgery i.e. laparotomy, today surgery often can be performed hysteroscopically or laparoscopically by suitably skilled endoscopic surgeons. This newer approach to surgery dramatically reduces hospitalisation and recovery time. In addition a newer but still experimental approach for infertile patients, involves blocking the blood vessels supplying the fibroids i.e. “Embolisation”.
In select cases a myomectomy could lead to some improvement in ART success rates.
c) Tubes & Ovaries
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Surgery is recommended to correct certain types of problems affecting tubes and ovaries. The decision to undertake this form of therapy is not easy, and your doctor will advise you. The delicate type of surgery undertaken on tubes and ovaries is called microsurgery and fertility experts require specific training in this specialised field. Only trained microsurgeons should therefor correct these problems and the patient should confirm this prior to undergoing corrective surgery! Often the potential success of surgery must be weighed up against the success of ART and today most ART units have success rates so much better than those resulting from surgery, that surgery is seldom undertaken. However if ART is not available then surgery may be a good alternative. Certain types of microsurgery can be performed via the laparoscope however you may have to be referred to a specialist unit for this.
Tubal ligation and approach to restoring fertility
Patients may request the reversal of a tubal ligation. Tubal ligation is a general term describing many different types of surgical procedures to block a woman’s Fallopian tubes in order to sterilise them. Surgical reversal of this type of operation once again depends upon a number of factors including the woman’s age, the type of sterilisation procedure performed, the overall fertility of the couple and the fertility expert’s skill at microsurgery to mention a few. The IVF option does not require functional Fallopian tubes. Further information should be obtained from your fertility specialist.
At present rather than undertaking open surgery (laparotomy) in the form of microsugery, when required it can be undertaken by laparoscopy, which is far less invasive than open surgery, and equally as effective.
Removal of Blocked tubes for IVF
One cause of infertility is blocked Fallopian tubes filled with fluid called hydrosalpinges. This problem is treated by IVF. It has been found that removal or blocking off of these tubes can increase IVF success rates by up to 40%. These procedures should be discussed with your fertility specialist specially if IVF has not been successful and you suffer from this problem.
Finally, other forms of surgery, such as wedge resections of ovaries (cutting a piece out), laser), ventrisuspension and ventrifixation (changing the position of the. uterus) should rarely, if ever, be performed, as complications of these operations usually outweigh any potential benefits.