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  » Infertility  »  Infertility and Endometriosis

Infertility and Endometriosis

Background

The endometrium is the tissue that lines the inside of the uterine cavity. Endometriosis is a disease state in which some of this tissue has spread elsewhere - such as to the ovaries, or elsewhere in the abdominal cavity.

Endometriosis causes pain in some women and can also cause infertility .

5-10% of all women have endometriosis. Most of these women are not infertile.

30-40% of infertile women have endometriosis.

Diagnosis of endometriosis

The only way to be sure whether a woman has endometriosis is to perform a surgical procedure called laparoscopy that allows us look inside the abdominal cavity with a narrow scope.

Sometimes we bly suspect that the disease is present based on the woman's history of very painful menstrual cycles, painful intercourse, etc., or based on the physical examination of the woman or ultrasound findings.

Mild endometriosis

Endometriosis of the ovary and peritoneum Brown endometriosis spots on pelvic side wall

The large majority of cases of endometriosis are mild.

Women with any stage of endometriosis (mild, moderate, or severe) can have severe lower abdominal and pelvic pain - or they might have no pain or symptoms whatsoever.

Although mild endometriosis is associated with infertility in some women, many fertile women also have mild endometriosis. A cause and effect relationship between mild endometriosis and infertility has not been established. It might be that infertility and delayed pregnancy predisposes women to developing endometriosis, rather than the endometriosis causing the infertility.

Therefore, some experts consider infertility associated with mild endometriosis to really be "unexplained infertility".

Severe endometriosis

Severe endometriosis causes pelvic scarring and distortion of pelvic anatomy. The tubes can become damaged or blocked and the ovaries often contain cysts of endometriosis (endometriomas) and may become adherent to the uterus, bowel or pelvic side wall. Any of these anatomic distortions can result in infertility.

In some cases the eggs in the ovaries can be damaged, resulting in decreased ovarian reserve and reduced egg quantity and quality.

Treatment of endometriosis

Treatment for endometriosis associated with infertility needs to be individualized for each woman. There are no easy answers, and treatment decisions depend on factors such as the severity of the disease and its location in the pelvis, the age of the woman, length of infertility, and the presence of pain or other symptoms. Some general issues regarding treatment are discussed here:

Treatment for mild endometriosis

Medical (drug) treatment can suppress endometriosis and relieve the associated pain in many women. Surgical removal of lesions by laparoscopy might also reduce the pain temporarily.

However, several well-controlled studies have shown that neither medical or surgical treatment for mild endometriosis will improve pregnancy rates for infertile women as compared to expectant management (no treatment). There are a few more recent studies that did show a benefit to surgical treatment of mild endometriosis. This is interesting because previous studies have shown no benefit.

For treatment of the infertility associated with mild to moderate endometriosis, controlled ovarian hyperstimulation with intrauterine insemination is often attempted and has a reasonable chance to result in pregnancy if other infertility factors are not present.

If this is not effective after about 6 cycles (maximum), then in vitro fertilization should be considered.

Treatment for severe endometriosis

Several studies have shown that medical treatment for severe endometriosis does not improve pregnancy rates for infertile women.

Some studies have shown that surgical treatment of severe endometriosis does improve the chances for pregnancy as compared to no treatment. However, pregnancy rates remain low after surgery - some studies have reported pregnancy rates of 1.5-2% per month.

Some physicians advocate medical suppression with a GnRH-agonist such as Lupron, Synarel, or Zoladex for up to 6 months after surgery for severe endometriosis before attempting conception. Although at least one published study found this to improve pregnancy rates as compared to surgery alone, other studies have shown it to be of no benefit. This is one of many issues regarding endometriosis that there is not universal agreement about among infertility specialists.

Unfortunately, the infertility in women with severe endometriosis is often resistant to treatment with ovarian stimulation plus intrauterine insemination. If the pelvic anatomy is very distorted, insemination would probably be futile. These women will often require in vitro fertilization in order to conceive.

Although the studies of in vitro fertilization for women with severe endometriosis do not all show similar results, pregnancy rates are usually good if the woman is relatively young (under 40) and if she produces enough eggs during the ovarian stimulation

In vitro fertilization - IVF

What is in vitro fertilization?

IVF involves taking eggs from the woman, fertilizing them in the laboratory with her partner's sperm and transferring the resulting embryos back to her uterus 2-6 (usually 3 or 5) days later.

The first IVF baby in the world was born in July of 1978 in England . Today, many thousands of children are born annually as a result of this technique.

In vitro fertilization involves stimulating the woman with medications, taking a number of eggs from her ovaries, fertilizing them with her husbands sperm and transferring some of the resulting embryos back into her uterus with the hope that one will implant. There is detailed information elsewhere on this site about in vitro fertilization .

The biggest advantage of IVF is that the woman avoids the tubal reversal surgery. Another advantage is that the outcome is known 10 days after the procedure when we do the first pregnancy test rather then waiting for a year or more to find out whether the procedure is successful. Success rates with IVF vary greatly according to the program. Some IVF programs have pregnancy rates with tubal factor infertility of over 50% per attempt in women under 40 years old. Other programs with the same type of patients report pregnancy rates of only 20 to 30% (or sometimes less). The reason for this is that some IVF programs are better than others. This is why the couple should do some careful comparisons before choosing an IVF program.

The biggest disadvantages of IVF are that the woman has to take medications to stimulate development of multiple eggs and that there is always some risk for multiple pregnancy - although this can be controlled by limiting the numbers of embryos transferred to 2 (or 3). Another disadvantage is that if the first attempt does not work the couple must try again and unless there were left over embryos that were frozen the cost for the repeat cycle would be the same as the initial cycle.

Who should be treated with in vitro fertilization?

In vitro fertilization can be used as an effective treatment for infertility of all causes except for women with infertility caused by an anatomic problem with the uterus , such as severe intrauterine adhesions.

It is generally used in couples who have failed to conceive after at least one year of trying who also have one or more of the following:

1. Blocked fallopian tubes or pelvic adhesions with distorted pelvic anatomy. Women that have had tubal ligation and are considering tubal reversal surgery as well as men that are considering vasectomy reversal surgery might also consider IVF. 
2. Severe male factor infertility (low sperm count or low motility) 
3. Failed 2-6 cycles of ovarian stimulation with intrauterine insemination  
4. Advanced female age - over 38
5. Reduced ovarian reserve , which means lower quantity (and sometimes quantity) of eggs. A day 3 FSH and estradiol test and antral follicle counts are often done as screening tests for egg quantity (and quality). Reduced egg quantity and quality is usually treated with either IVF, or with IVF using egg donation from another woman.
6. Severe endometriosis

Details about the injectable medications for in vitro fertilization

Subcutaneous Fertility Shots

 

Mixing Sub-Q Meds

Intramuscular Fertility Shots

 

Sample IVF Calendar

In order to get sufficient eggs for the in vitro fertilization process, the woman is stimulated with injected medications to develop multiple egg development. The injections are usually done by the woman, or by her husband. The technique is easy to learn.

Usually, 2 different injectable medications are used in IVF cycles. One of these can be replaced in some cases by a nasal spray.

The first medication starts on about day 21 of the woman's cycle and is called Lupron. The purpose of this medicine is to "down-regulate" the pituitary gland with regard to production of FSH and LH. This allows us to have more complete control of the subsequent stimulation of the ovaries. This medicine is given as a subcutaneous injection with a small needle and is usually given into the thigh. These injections continue for about 14-25 days.

The woman will get her period at the normal time (day 28, or whatever, of her cycle).

The next medication begins a few days after her period starts. This is the FSH (follicle stimulating hormone) that will stimulate the ovaries to produce multiple eggs. There are several name brands available - some can be given as subcutaneous injections , while others must be given as intramuscular injections . Examples are Gonal-F, Follistim, Humegon, Repronex and Fertinex.

Once the FSH injections have begun, blood and ultrasound testing is done about every 1-3 days to monitor the development of the follicles (egg-containing structures) in the ovaries.


Ultrasound of multiple follicles (3 black circles) in a stimulated ovary

When the woman's follicles are mature, an egg aspiration procedure is performed to remove the eggs from her ovaries.

Sample calendar for an injectable FSH cycle. These infertility treatment cycles are often referred to as controlled ovarian stimulation (or, hyperstimulation) cycles. Injectable FSH products are also referred to as HMG, human menopausal gonadotropins, or gonadotropins. Brand names for these drugs (hormones) in the USA include Pergonal, Follistim, Gonal-F, Repronex and Humegon.
A sample showing the days medications are taken and approximate timing of the monitoring of ovarian stimulation and intrauterine insemination procedure.

Sunday

Monday

Tuesday

Wednesday

Thursday

Friday

Saturday

1

Menstrual period starts

2

3

Baseline blood and ultrasound

Day 1 of stimulation

Start FSH shots

4

Day 2 of stimulation

FSH shot

5

Day 3 of stimulation

FSH shot

6

Day 4 of stimulation
FSH shot

7

Blood and ultrasound

Day 5 of stimulation


FSH shot

8

 

Day 6 of stimulation

FSH shot

9

Blood and ultrasound

Day 7 of stimulation

FSH shot

10

Day 8 of stimulation

Stimulation is done - HCG "trigger" shot given in evening

11

12

 

Insemination (or timed intercourse) in morning

13

14

Key to table:

Blood and ultrasound = blood test for hormone levels and transvaginal ultrasound to measure follicle development in ovaries

FSH = subcutaneous injection of a medication containing follicle stimulating hormone (FSH), which causes follicles containing eggs to develop in the ovaries.

HCG "trigger" shot = injection of a medication called HCG, which causes the eggs to complete the maturation process. This is taken only once in the cycle. Release of the eggs should occur about 36-46 hours after the shot.

Note:

The calendar shown above is an example of how the cycle stimulation may evolve. However, some women will need to be monitored more often than shown above. Particularly if they have polycystic ovaries and irregular menstrual cycles.

The duration of stimulation is usually about 8 days, but ranges from about 5 days to about 14 or more days.

Details about the intramuscular injections used for infertility and in vitro fertilization

MEDICATION MIXING INSTRUCTIONS
PREPARING INTRAMUSCULAR (IM) INJECTIONS USING VIALS


Remove the syringe and needle from the wrapper, making sure needle is secure. Set aside.

Remove plastic caps from prescribed # of vials of medication and diluent.

Wipe tops of vials with alcohol to sterilize them. Don't touch the tops after they have been cleansed.

Uncap needle by pulling cap straight out. Do not twist.

Draw up 2cc of air into syringe and inject into each powdered vial.

Draw up 2cc of air and inject into the diluent vial. Tip the diluent vial and, with the needle in the fluid, withdraw fluid to the 2cc mark. Remove needle from vial.

Inject the diluent fluid into the vial of powder, gently aiming the fluid at the side of the vial.

The powder will dissolve quickly-do not shake the vial. This will create bubbles.

After the powder has dissolved, draw the reconstituted solution into the syringe. This can be done in 2 ways:

  1. Leave the vial on the counter, tilting the vial at the end, to withdraw the full solution.
  2. After inserting the needle, raise the vial upside down to withdraw the medication. Slowly lower the needle as you withdraw the full solution.

If you are instructed to reconstitute 2-4 vials, simply take your filled syringe, insert the needle into the rubber stopper of the second vial, and inject the reconstituted mixture. Withdraw the fluid as described previously. Repeat this procedure for each vial up to 4. If you are taking more than 4 vials at a time, they must be divided up into 2 shots.

After drawing up the last vial of medication, carefully recap the needle. Change the needle to the blue 25G 1 1/2 inch needle.

If the uncapped needle ever comes into contact with anything but the medication or diluent in the vial, such as your finger or countertop, immediately remove the needle and replace it with a new one.

Next, hold the syringe straight up and tap it so that any air bubbles rise to the top. To get rid of the bubbles, slowly press the plunger just a little, until a drop of liquid forms at the tip of the needle.

You are now ready to give your injection.

ADMINISTRATION OF INTRAMUSCULAR INJECTIONS
Injection Instructions: General Comments

Humegon, Metrodin, Pergonal, Repronex, HCG and progesterone in oil need to be administered intramuscularly into the large muscle of the buttock
To locate the correct area, divide the buttock into four parts. The injections should be given in the upper, outer portion of the buttock, please note picture:
The needle should go into the skin on a 90 degree angle, and should go into the skin the entire 1½ inches (entire length of needle)
A consistent even motion should be used when an injection is administered

The woman who is getting the injection should lay face down on a bed or lean over the bed

INJECTION INSTRUCTIONS

Wash hands

Cleanse injection site with an alcohol pad in a circular fashion

Check correct area for injection

Remove cap from needle

Hold syringe like a pencil or dart on a 90 degree angle to the skin

Use a single consistent motion when breaking the skin. A slow dragging motion will increase the discomfort of the injection.

The entire 1 ½" needle must enter the muscle

When the needle is in the muscle, steady the syringe with one hand, pull back on the plunger to look for possible blood in the syringe ( this would indicate that the needle is not in the correct area). Should this occur, simply remove the needle and find a new site for the injection. You may use the same medication. Attach a new needle.

If after pulling back on the plunger no blood was noted, (remains clear) slowly push on the plunger to administer the entire contents of medication in the syringe.

Pull the needle straight out quickly.

Some blood may appear at the surface of the skin.

Place a Band-Aid at the injection site.

Dispose of all needles in a safe manner by using a special container (glass bottle or empty pop can).

Gently massage the area.

Details about the subcutaneous injections for infertility and in vitro fertilization

The woman is stimulated with subcutaneously injected medications to develop multiple egg development. Subcutaneous injections are given with a very small needle, just under the skin. This is how diabetics give themselves insulin.

Usually, 2 different injectable medications are used in IVF cycles. One of these can be replaced in some cases by a nasal spray. Details about ovarian stimulation for IVF are available elsewhere on this site.

The first medication starts on about day 21 of the woman's cycle and is called Lupron. This is a subcutaneous injection with a small needle and is usually given by the woman into her thigh. She will usually take this once a day for about 21 days.

The next medication is injectable FSH and is usually taken for about 9 days. This medication stimulates multiple eggs to develop. There are various subcutaneously given FSH products available in the US including Follistim, Gonal-F and Fertinex. Other FSH products are available that must be given intramuscularly with a larger needle, e.g. Pergonal, Humegon, Repronex and Metrodin.

Read below for details on giving the subcutaneous injections

SUBCUTANEOUS ADMINISTRATION OF LUPRON, GONAL-F, FOLLISTIM, FERTINEX, HUMEGON, REPRONEX, etc.

Choose your injection site (abdomen, thigh, or back of upper arm)

Cleanse the site with alcohol, beginning at the center of the site and moving outward in a

circular motion. Allow the skin to dry before injection to avoid a stinging sensation.

Remove needle cover being careful not to loosen the needle from the syringe.

Grasp the syringe like a pencil. Squeeze the skin and position the needle at a 90 degree

angle to the skin surface.

Insert the needle quickly with a dart-like motion.

Pull back slightly on the plunger to check for blood. If none, inject the drug by pushing on the plunger. If blood appears, withdraw the needle entirely. Change the needle, prepare a new site and inject again.

After injecting the medication, let go of the pinched skin and remove the needle gently but quickly. If any bleeding occurs from the site, apply gentle pressure for 10 to 15 seconds.

Alternate injection sites.

Dispose of syringe in a glass jar or other appropriate container. Return your used needles to the office at the end of your cycle for us to dispose of.

Ultrasound of multiple follicles (black circles) in a stimulated ovary

When the woman's follicles are mature, an egg aspiration (retrieval) procedure is performed to remove the eggs from her ovaries.


4 cell embryo from IVF