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Comprehensive Female Fertility Evaluation

With 50% of difficulty with conception being related to the female and up to 35% of couples having more than one problem, being offered and completing the entire work-up is critical, to make sure nothing is missed or overlooked, no matter how small or unlikely the possibility may be. At Arizona Center for Fertility Studies, the work-up is divided into three stages, with each stage being equally important. Prior to any evaluation, a complete medical history, physical examination and review of any pertinent medical records is essential. 80-90% of the time, the cause of female infertility can be identified; and successfully corrected, tricked or "get around-able". "When it is all said and done, successful treatment boils down to four words... quality of the egg".

Normal Female Anatomy

Graphic representation of normal female anatomy

Also, all women attempting pregnancy are placed on prenatal vitamins, mainly because of the folic acid, which has been shown to reduce birth defects by one half and spina bifida, or the open spinal cord in the baby by two-thirds; and omega-3 fatty acids, that have been shown to maximize the baby's eye and brain development and fetal growth.

STAGE I FERTILITY EVALUATION

Hysterosalpingogram (HSG)

Hysterosalpingogram (HSG) is an x-ray of the uterus and fallopian tubes to mainly check to see if the tubes are open and there is no scar tissue at the ends. It also can identify any abnormalities of the uterine cavity like a double uterus, polyps or fibroids. It is done between days 7-11 of the cycle and generally at a radiologist's office. The test takes about 10-15 minutes and can sometimes be associated with some cramping, especially if the fallopian tubes are blocked at either end. You may even have some spotting or light bleeding after the test but it should stop within several hours. An hour or so prior to the test, you can take 800 mg of Motrin or Advil or 2 tablets of Alleve. If you are concerned that the test may be "painful" or you are anxious, Arizona Center for Fertility Studies can prescribe a Percocet and/or Valium to take an hour or so before the test (but make sure someone can drive you and don't make any plans for the rest of the day). A small catheter is placed through the cervix and into the uterus and than a radio-opaque water soluble dye is slowly injected allowing the uterus to be outlined and the tubes to fill and spill freely into the pelvis.

Most radiology clinics charge $800-$900 for this test but Arizona Center for Fertility Studies has worked out a price of $200 with 2 clinics.

Tubal factors make up 20-40% of the causes of infertility in women and can be due to previous pelvic inflammatory disease, previous infection from gonorrhea or chlamydia, previous tubal surgery, ruptured appendix, endometriosis and known or unknown infections following childbirth.

Hysterosalpinogram

Hysterosalpingogram (HSG) showing radio-opaque dye filling the uterus and both fallopian tubes.

Sonohysterogram (SHG)

Sonohysterogram (SHG) is a test where a small catheter is placed through the cervix and into the uterus, similar to an hysterosalpingogram (HSG). Water is then slowly injected into the uterus and transvaginal ultrasound is done to evaluate the uterine cavity.

In Arizona Center for Fertility Studies experience, a Sonohysterogram (SHG) is much more accurate than a Hysterosalpingogram (HSG) in evaluating the uterine cavity for abnormalities like a bicornuate or septate uterus (double uterus) and to rule out any filling defects in the cavity like a polyp or fibroid, that can be overlooked on a Hysterosalpingogram (HSG).

Arizona Center for Fertility Studies has found that it is not uncommon for the Hysterosalpingogram (HSG) to show a normal uterine cavity, but the Sonohysterogram (SHG) will show a filling defect. The Hysterosalpingogram (HSG) is very good at evaluating whether or not the fallopian tubes are open, but Arizona Center for Fertility Studies will always recommend a Sonohysterogram (SHG) to be "sure" not to overlook a filling defect that could affect a woman getting pregnant or result in a miscarriage (Diagnostic Hysteroscopy). It can be done, basically anytime in the cycle, as long as a pregnancy waiver is signed. It is done in the office at Arizona Center for Fertility Studies and takes about 15 minutes. It is associated with little to no discomfort and generally the patient does not have to take any pain medication. Antibiotics are given prophylactically before and after the test.

Sonohysterogram

Sonohysterogram (SHG) of an intrauterine filling defect, showing either a polyp or fibroid. Diagnosis is made at hysteroscopy and removed by morcellation.

Post-Coital Test (PCT)

Although an older test and in many clinics not done anymore; a Post-Coital Test (PCT) checks a woman's cervical mucus-sperm interaction. Only around ovulation is a woman's cervical mucus good and receptive to sperm, which generally is a small window of 2-3 days. The test can be timed by an over the counter ovulation detection kit (ODK) being positive or by transvaginal ultrasound to measure when the egg follicle is mature, both indicating that ovulation is imminent. The couple is then asked to make love and is seen 2-12 hours later. Sperm can live in the cervical mucus for 3-4 days and there is evidence of sperm living up to, as long as, 10 days. After intercourse, in patients with good cervical mucus, sperm have been found in the fallopian as soon as 3 minutes. The test is done by placing a speculum and cervical mucus is then collected in a small syringe, examined for clarity and stretchiness (spinnbarkeit), and placed on a slide under the microscope. The mucus is than checked for the number of sperm seen per high powered field, percentage of motility or movement of the sperm and the number of normal appearing sperm (morphology). Although, there can be many interpretations of what is a normal Post-Coital Test (PCT), and hence the controversy, Arizona Center for Fertility Studies feels that the test is simple, painless and inexpensive, and gives valuable information about sperm-mucus interaction, which is responsible for 15-20% of the causes of infertility. Anything that damages the cervix can cause an abnormal Post-Coital Test (PCT) including cervical and vaginal infections, cryosurgery or cautery for an abnormal PAP smear, cervical conization, LEEP procedure, DES exposure, the use of Clomid for ovulation and the normal hormonal flux of the vagina.

Post Coital Test

Graphic representation of the mechanics of doing a Post-Coital Test (PCT)
Normal and Abnormal Post-Coital Test (PCT)

Evaluation and interpretation of a normal and abnormal post-coital test

Endometrial Biopsy (EMB)

Also an older test and not recommended by many clinics anymore, an Endometrial Biopsy (EMB) tests whether the uterine lining is preparing itself adequately for implantation of the embryo. The test is done several days before the onset of the menstrual cycle (usually cycle day 25-26). A small plastic instrument, called a Pipelle, is inserted through the cervix and into the uterine cavity where a very small piece of endometrial lining is removed by pulling back on the center piece of the Pipelle and creating a weak suction. The tissue is then sent to pathology to be evaluated for which day in the cycle the lining of the uterus is at. That is then compared to where the woman is chronologically in her cycle. The two have to be read within 1-2 days of each other, or the lining is out of phase, known as a luteal phase defect, which can prevent implantation from occurring or result in an early miscarriage. An abnormal Endometrial Biopsy (EMB) is treated with progesterone lozenges, suppositories or intramuscular shots. If these are not successful, then HMG has been shown to be very effective in correcting the abnormal Endometrial Biopsy (EMB). The test can be interpreted differently by different pathologists, and hence the controversy. An Endometrial Biopsy (EMB) at Arizona Center for Fertility Studies is always read by the same pathologist and he is either consistently right or consistently wrong, but at least he is consistent. Arizona Center for Fertility Studies feels that the test still has value in evaluating why a couple is having trouble conceiving, if taking Clomid has altered the uterine lining preparation, in diagnosing a luteal phase defect which can increase the risk of a miscarriage, or as part of the evaluation for repeated pregnancy loss. At Arizona Center for Fertility Studies, the test is associated with little discomfort and the literature does not show an increased risk of miscarriage if you were to be pregnant (even though Arizona Center for Fertility Studies will ask you to sign a waiver).

Semen Analysis (SA)

Since 50% of the causes of infertility are due to the male, a complete Semen Analysis (SA) is very important. The test is usually done by having the partner collect a masturbated sample after abstaining from intercourse for 2-3 days. The sample is ejaculated into a sterile container, usually a sterile wide mouth urine cup, either at home or in the office and then evaluated for sperm numbers, motility, morphology, volume, clarity and time to turn from a gel to a liquid. Fifty percent of men are comfortable collecting a sample in the office, the other 50% would prefer collecting at home. There is no disadvantage of collecting a sample at home and the sample can be brought to the office within an hour. Occasionally, a man is not comfortable with masturbation and, if that is the case, then Arizona Center for Fertility Studies can provide him with a sterile condom, that can be used during intercourse, to collect the sample. When doing a SA it is important that the morphology be done by strict Krueger's morphology testing. This is where the sperm are inactivated on a slide, stained, and carefully examined for normal morphology. At most outside labs, like LabCorp or Sonora Quest, strict Krueger morphology testing is not done and thus, there is a wide interpretation of the percentage of normal sperm morphology.

Arizona Center for Fertility Studies works with many valley urologists that specialize in reproductive services.

STAGE II FERTILITY EVALUATION

Thyroid Stimulating Hormone (TSH)

Thyroid testing is important and if abnormal can either prevent pregnancy or increase the risks of a miscarriage. Thyroid Stimulating Hormone (TSH) is the most sensitive of all the thyroid testing and is elevated in patients with hypothyroidism and decreased in patients with hyperthyroidism. Even if you do not have any symptoms of either hypo or hyperthyroidism, it is still important to measure Thyroid Stimulating Hormone (TSH) because, more commonly in women than men, Thyroid Stimulating Hormone (TSH) can be elevated without any symptoms of hypothyroidism. This is known as compensated hypothyroidism, where the thyroid gland is beginning to fail and as a result, the brain is sending more signals, Thyroid Stimulating Hormone (TSH), to stimulate the thyroid gland to keep up its production of thyroxine or T4. If overlooked and not treated, compensated hypothyroidism can cause infertility. The treatment is usually simple and requires the addition of thyroid medication, usually Synthroid, in low doses and rechecking the Thyroid Stimulating Hormone (TSH) levels to make sure they are back into the normal range. On the other hand, far too often, women are told by their treating physician that they have "mild" thyroid disease or low dose thyroid medication "may be helpful", and are started on thyroid medication, even though all their thyroid tests are normal, thinking that it will improve their fertility outcomes. In these circumstances, the thyroid medication will not increase their chances of success and may even cause them to become mildly hyperthyroid, which can have negative consequences on fertility outcomes.

Prolactin (PRL)

Prolactin is a hormone secreted by the pituitary gland during pregnancy and lactation. If it is elevated in a non-pregnant state, it can effect steroidogenesis or the production of estrogen and progesterone, causing problems with ovulation, implantation of the embryo, development of the uterine lining and an increased risk of miscarriages. An elevated Prolactin (PRL) level in a non-pregnant woman is generally due to microscopic benign adenoma (tumor) on the pituitary gland that stimulates that area of the gland to produce an excess amount of prolactin. If the prolactin level is elevated high enough, a woman will not have periods and/or will have white milky breast discharge from one or both breasts, either spontaneously or with expression. Other symptoms of a high prolactin level are headaches, dizziness, lightheadedness, feeling faint, spots in front of your eyes and even decreased sex drive (which is commonly seen in men with elevated Prolactin (PRL) levels). On the other hand, Prolactin (PRL) can be mildly elevated but menstrual cycles can be regular and there is no breast discharge. These are the patients that should not be overlooked because mildly elevated Prolactin (PRL) levels can definitively effect fertility outcomes. If the Prolactin (PRL) is elevated, it should be discussed with the patient, and she should understand that these microadenomas are always benign and rarely enlarge (they are extremely slow growing) and that "she does not have a brain tumor". Arizona Center for Fertility Studies has a tremendous amount of experience with evaluation and treatment of these microadenomas, and will only suggest a MRI if the prolactin level is above 60. Otherwise, the chance of seeing a microadenoma on the MRI is extremely low. The MRI is done to get a baseline reading, and even if a microadenoma is seen, it does not change the thinking or the treatment options. If the Prolactin (PRL) level is elevated, treatment is begun with Parlodel or bromocriptine, a dopamine like antagonist, which is very effective in quickly getting the prolactin level back into the normal range. If a woman cannot take Parlodel, for whatever reason, there is another medication, Dostinex, that can be used instead; however, it is more expensive and is only taken twice a week, so sometimes a little harder to remember to take.

The medication, ideally needs to be started before a woman gets pregnant, and should be continued through the first 8 weeks of pregnancy. The literature shows there are no adverse effects of Parlodel in early pregnancy and stopping it too soon may increase the chance of miscarrying. Prolactin levels normally rise during pregnancy and if you have a history of an already elevated level of Prolactin (PRL), your OB needs to monitor the prolactin levels monthly during the rest of the pregnancy, and if the Prolactin (PRL) levels get too high for that stage of pregnancy, than Parlodel may have to be restarted to keep the prolactin levels in the normal range. These prolactinomas, as they are sometimes called, are common in women in reproductive age, and are only tested for as part of a work-up for infertility. Any woman with irregular cycles or difficulty with conceiving should automatically be tested for prolactin.

Antiphospholipid Antibodies (APA)

Antiphospholipid antibodies are antibodies against the fatty part of the blood vessel wall and, if elevated, can prevent pregnancy or increase the risk of a miscarriage. All blood vessel walls are made up of fatty cells known as phospholipids. In some women, especially those having problems conceiving, there is the production of antibodies against these phospholipids, or antiphospholipid antibodies or Antiphospholipid Antibodies (APA). These antibodies can attack the blood vessel wall and damage it. Any time a blood vessel wall is injured it heals by making a small clot that patches the wall and begins the healing process. In the major blood vessels of the body, these micro-insults and micro-clots are of no consequence, but in the small tiny blood vessels of an early developing pregnancy, the clot can be larger than the blood vessel and hence block off blood flow to the pregnancy, resulting in losing the pregnancy between ovulation and your period or worse, miscarrying between 6-8+ weeks when there is an increase demand for blood flow for nutrients to the baby and most of the blood vessels are blocked off. Testing is controversial and most clinics do not test for Antiphospholipid Antibodies (APA) unless you have a history of repeated pregnancy loss, in which case, you may test positive for these antibodies. The argument is that fertile women can also test positive for Antiphospholipid Antibodies (APA) and yet have no problems with conception or carrying a pregnancy to term. This is true, although, almost all programs will not do the test until after you have 2 or more pregnancy losses. Why wait until you have 2 documented pregnancy losses before doing the test' Arizona Center for Fertility Studies believes it is better to be proactive than reactive and strongly recommends Antiphospholipid Antibodies (APA) as part of the initial work-up; not to mention the emotional and physical trauma of losing 2 or more pregnancies that possibly could have been prevented.

Antisperm Antibodies (ASA)

Antisperm antibodies are antibodies against human sperm, and not specifically, the woman's partner. They are elevated in 1-6% of women having difficulty with conceiving. If elevated, these Antisperm Antibodies (ASA) may bind with sperm anywhere in the reproductive tract; vagina, cervix, uterus or fallopian tube, and thus immobilize them, resulting in the sperm's inability to fertilize the egg. There is also evidence to suggest that Antisperm Antibodies (ASA) can attach to the paternal contribution and the embryo, and thus increasing the risk of a miscarriage. This test, like Antiphospholipid Antibodies (APA), is also controversial. There are a small percentage of fertile woman who test positive for Antisperm Antibodies (ASA) but have no trouble with conceiving or carrying a pregnancy to term. However, if you are having difficulty with conceiving, thinking about doing IUI (intrauterine insemination) and/or have a history of repeated pregnancy loss, Arizona Center for Fertility Studies feels strongly that this test should be done, and, if positive, the woman should be given the choice for treatment or not to put sperm in the reproductive tract and think about the option of putting embryos in instead. The treatment is low dose prednisone, that sometimes is very effective in lowering the percentage of antibodies against the sperm, and thus allowing for natural conception or to proceed with IUI and not have to worry about the possibility that the Antisperm Antibodies (ASA) will attack the sperm. At Arizona Center for Fertility Studies, antisperm antibody testing is recommended as part of the initial evaluation.

Chlamydia Antibodies (CA)

Arizona Center for Fertility Studies does not do chlamydial cultures on women. In our opinion it is a bit insulting and has no practical clinical value. By doing a chlamydia culture on a woman who is married or in a committed relationship, on some level, you are saying that you do not trust her (or her partner) and that one of them has chlamydia and you want to document that is not true. Arizona Center for Fertility Studies is willing to say that rarely would one of their patients test positive on a chlamydia culture and therefore, at Arizona Center for Fertility Studies, it is not done. On the other hand, Arizona Center for Fertility Studies does recommend chlamydia antibody testing on everyone, unless they have had a known history of chlamydia exposure, in which case the Chlamydia Antibodies (CA) testing would be positive or if a couple are each other's only partner ever. If the Chlamydia Antibodies (CA) testing is positive, it indicates that sometime in the patient's past that she was exposed to chlamydia. Most will say that they have never been exposed to or have had a STD. The problem with chlamydia, unlike gonorrhea, is that 50% of the time the symptoms are silent and the woman never knows that she was exposed. Symptoms could be non-existent or present as some mild cramping, making her think that she is having an early period or maybe something bad that she had eaten. The importance of measuring Chlamydia Antibodies (CA) is that every exposure to chlamydia is associated with a 25% chance of tubal damage that could lead to scar tissue and adhesions, which could prevent pregnancy; or, if positive, not necessarily prevent pregnancy, but increase the risk of an ectopic pregnancy. On a positive note, 75% of the time, the chlamydia exposure does not cause any tubal damage. Any woman with a positive Chlamydia Antibodies (CA) who gets pregnant, is at increased risk of an ectopic pregnancy, and should get an early pregnancy test and, if positive, an early ultrasound to document that the pregnancy is in the uterus. If the entire work-up is negative, except for the finding of positive chlamydia antibodies, then before proceeding with other treatment options, a diagnostic laparoscopy needs to be discussed to look into the abdomen and evaluate the pelvis for scar tissue and adhesions. If intrauterine insemination (IUI) is done and there are pelvic adhesion, than it may not be successful and you could be wasting time and money. At Arizona Center for Fertility Studies, chlamydia antibodies are recommended as part of the initial evaluation, and a chlamydia culture is only done if the chlamydia antibody test is positive.

Mycoplasma Cultures

Mycoplasma is a less known bacteria that is associated with infertility and repeated pregnancy loss. It is generally sexually transmitted, can lay dormant in the cervix for long periods, and many times, is not associated with any symptoms. The thinking is that the mycoplasma bacteria may bind with sperm or even the early developing embryo causing a mycoplasma-sperm complex or mycoplasma-embryo complex that white cells will attack and destroy thus inhibiting pregnancy or increasing the risk of a miscarriage. The treatment is simple and straightforward. If the woman tests positive, then she and her partner are treated with either doxycycline (long acting tetracycline) or erythromycin for three weeks, asked to refrain from intercourse or use a condom during that time and then get retested 1-2 weeks after treatment is finished. In most labs, when mycoplasma cultures are done, the laboratory also tests for ureaplasma. Ureaplasma is a very uncommon bacteria but searching through the old, and even recent literature, you can find references to the fact that ureaplasma has been associated with infertility and pregnancy loss. The treatment is the same as mycoplasma, and the thinking at Arizona Center for Fertility Studies is, that even if there is a 1% chance that ureaplasma can effect treatment outcome, it should be treated. Since that treatment using doxycycline or erythromycin is easy and has few to no side effects, Arizona Center for Fertility Studies will treat any patient testing positive for ureaplasma.

Cystic Fibrosis Testing (CF)

Cystic fibrosis testing is recommended by the American College of Obstetrics and Gynecology but, at Arizona Center for Fertility Studies, it is optional and only recommended for woman that are at increased risk.

As you can see, after reading about the work-up and evaluation of the female, there are a number of tests that cross-over with the evaluation of repeated pregnancy loss; and therefore, is another reason why Arizona Center for Fertility Studies feels strongly that a complete work-up is so important.

STAGE III FERTILITY EVALUATION

Stage III are tests recommended by the American College of Obstetrics and Gynecology, a society committed to the protection of the woman and her unborn child. These tests include:

  • HIV
  • Hepatitis B (HBV) and C (HCV)
  • RPR - A test for syphilis
  • Rubella or german measles
  • Varicella or chicken pox

Why Rubella and Varicella?

It has been shown that woman can lose their immunity to german measles and/or chicken pox, even if they were exposed as a child or received the vaccine in the past. If a woman's immunity is lost, then that means she is susceptible, if exposed, to getting german measles and/or chicken pox. Both viruses can cause serious birth defects; and if exposed and infected, the strong recommendation is to terminate the pregnancy. With more and more parents electing not to vaccinate their young children with the MMR because of the "possible" increase risk of autism, more children are going to be exposed to and get german measles. It is generally a benign viral illness for the child, but it will put more pregnant woman at risk, especially those that have lost your immunity. If a woman tests negative for either rubella and/or varicella, meaning she has lost her immunity, the options are to be very careful and avoid children that could be infected; or, to take a vaccine. The down side of the vaccine is that you cannot attempt pregnancy for a month; the upside, is you do not have to worry about exposure.

Why Hepatitis B?

The bad hepatitis is C (HCV), and with a 5-12% risk of transferring the hepatitis C virus to the baby; women will not attempt pregnancy until they are treated. On the other hand, a woman can be exposed to hepatitis B and never know it. The infection can present with only flu-like symptoms. Arizona Center for Fertility Studies recommends that all women be tested for the hepatitis B core antibody, which tells if she has had a previous exposure. The test is has two parts. The first is HBV-IgG which, if positive, indicates that the woman has been exposed to HBV in the past. The other is HBV-IgM, which if positive, suggests a current infection from hepatitis B. If HBV-IgG is positive and HBV-IgM is negative, it means that the woman has had a previous exposure but currently has no evidence of any HBV in her body. So why do the test? Perinatologists (doctors that take care of newborn infants) believe that even though HBV-IgM is negative, there still may be hepatitis B viruses in the body, below the level of clinical laboratory detection, and during pregnancy can pass to the baby. Although the woman's immune system can easily fight off this "small amount of virus", the baby's immune system is not well developed and thus would potentially expose the infant to hepatitis B. The recommendation, if this is the case, is to vaccinate the newborn for hepatitis A and B, and give gammaglobulin, at birth.

An additional test that is recommended is a day 2-3 FSH level that checks for ovarian reserve and ovarian resistance. Although Arizona Center for Fertility Studies does day 3 FSH testing, it generally does not react to the results.

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