Female Infertility FAQs
Can my doctor increase my dose of clomiphene citrate so that I’ll ovulate more than one egg?
Clomiphene citrate (CC) therapy is one infertility treatment option at our Sacramento-area practice. CC is a very effective fertility medication for stimulating the ovary to ovulate in those patients who are not ovulating regularly. It acts by indirectly stimulating the pituitary (via its anti-estrogen action) to make more follicle stimulating hormone (FSH), which is responsible for stimulating follicular growth and development. When we use CC, we give enough to make a patient have a normal ovulatory cycle. We feel that increasing the dose beyond that point is not helpful in most cases. Increasing the dose rarely increases the number of eggs produced in most patients, and higher doses of CC can result in more severe anti-estrogen effects on the endometrial lining and cervical mucus that may actually interfere with conception.
What is the clomiphene citrate challenge test (CCCT)?
The CCCT is a test that we use to help to predict a woman’s reproductive or fertility potential. The tests consists of determination of follicle stimulating hormone (FSH) and estradiol levels in the blood on cycle day 3 and cycle day 10 (cycle day 1 is defined as the start of a period). Part of the test includes administration of an oral medication, known as clomiphene citrate at a dose of 100 mg (two tablets) daily from cycle day 5 through cycle day 9. Thus, the first set of laboratory testing is drawn just before beginning the clomiphene and the second set just after finishing the medication.
Who needs the CCCT?
We recommend the CCCT for all infertile women older than 35, and to younger women whose medical histories suggest poor ovarian function. This test is also useful for patients of any age with unexplained infertility.
How are the results of the CCCT interpreted?
Generally, an FSH level less than 10 mIU/ml is considered to be in the normal range. If the baseline (day 3) FSH is greater than 10 and/or the baseline estradiol level is elevated (greater than 70 pg/ml), the results are predictive of a significantly reduced fertility potential. The second set of lab testing (on day 10) is also important since approximately 50 percent of patients will have abnormal levels on day 10 only. FSH levels between 10 and 15 mIU/ml (on day 3 or on day 10) are in the “gray zone” in which pregnancy is still possible but is associated with a higher rate of miscarriage. An FSH level greater than 15 mIU/ml is indicative of a very low likelihood of pregnancy.
If my results are abnormal, what does that mean?
Studies have shown us that, in association with infertility treatment, more than 90 percent of patients with an abnormal CCCT will be unable to conceive and deliver a baby with their own eggs. This information helps us to identify patients who should probably forego ovulation induction and/or IVF in favor of egg donation or adoption.
Are there situations in which the CCCT is not as predictive of fertility potential?
Yes. Women with only one ovary tend to have slightly higher FSH levels. In addition, women who have had recent treatment with chemotherapy often have a temporary ovarian dysfunction with fluctuating FSH levels. Many of these patients will recover normal ovarian function and fertility potential as time passes.
How do you time inseminations? One doctor told me that it was necessary to perform the IUI on the day of ovulation.
When we treat a patient with clomiphene citrate and insemination, we instruct her to purchase an ovulation predictor kit and call us when her test is positive. On that day, a transvaginal ultrasound examination is performed to evaluate the follicle and the endometrial lining. If all looks good, the insemination is scheduled for the following day.
If a gonadotropin is being used, a spontaneous LH surge usually does not occur and once follicular maturity is reached, human chorionic gonadotropin (hCG) is given to induce ovulation. In these cycles, inseminations are scheduled for the two days following the HCG injection.
How soon after ovulation does the egg have to be fertilized, and how long do sperm live in the woman’s reproductive tract?
Following ovulation, the egg can “last” for some time (perhaps 12–24 hours) in an unfertilized state. If fertilization does not occur in that time period, however, the oocyte will die. Sperm will survive in the female reproductive tract for 24–72 hours. This time may be reduced somewhat for sperm that is washed and introduced to the woman’s reproductive tract through artificial insemination. Ideally, insemination should be performed as close to ovulation as possible. Insemination before ovulation is not necessary because the sperm do not need to traverse the cervical mucus. Because cervical mucus becomes essentially impenetrable to sperm just prior to ovulation (as a result of progesterone production), patients conceiving “naturally” must have intercourse the day before ovulation or earlier.
Blastocyst Culture and Transfer
What are blastocysts?
Blastocysts are embryos that are five to six days old and that have approximately 60 to 100 cells. This is the stage at which embryos hatch and implant in the uterine wall. With healthy blastocysts, an inner cell mass (that will develop into the fetus) as well as a blastocoel cavity surrounded by cells that are destined to form the placenta can be identified.
Why culture embryos to the blastocyst stage?
The longer the period of time that elapses between egg retrieval and embryo transfer, the easier it is to see differences between good and poor quality embryos. By day 5 after egg retrieval, embryos that have reached the blastocyst stage have distinguished themselves as the best quality embryos. Embryos that are not blastocysts by day 5 or 6 are poor quality and are destined to arrest in their development. Culturing embryos to the blastocyst stage allows us to transfer fewer embryos (usually two) while maintaining high rates of success. Thus the rate of multiple gestations can be reduced.
Is there any downside to blastocyst culture/transfer?
Yes. Some patients’ embryos may not grow to the blastocyst stage. Thus, these patients may not have any embryos to transfer on day 5 or 6. While many believe this is evidence for why a particular patient is unable to conceive, this outcome is very troublesome and unsatisfying for patients and for their physicians.
Who is a candidate for blastocyst culture/transfer?
In our program, we are offering blastocyst culture/transfer to patients at highest risk for a multiple pregnancy, including those being treated with IVF/donated eggs, and young patients (under age 35) who are doing IVF with their own eggs. Blastocyst culture/transfer may also be considered for patients of any age who have a large number of embryos. In all cases, we do not culture embryos beyond day 3 unless there are at least three high quality eight-cell embryos when the embryos are evaluated on that day.
Does blastocyst transfer increase pregnancy rates?
Not necessarily. It is very likely that the probability of implantation for a given embryo is not different whether it is transferred on day 3 or on day 5. Blastocyst transfer, however, helps us to choose the best embryos for transfer that may improve pregnancy rates.
IVF for Women over 40
How do you counsel women over 40 in regard to IVF?
When we discuss IVF with women over 40, we feel it’s important to clearly and honestly inform them of their chances for success. Because we know that fertility declines significantly with age, largely due to a decline in egg quality, it’s only fair that women over 40 understand the statistics. In our program, delivery rates are between 18 percent and 30 percent for women in their mid to late 30s, and about 15 percent for women 40 and 41 years of age. In our experience, it is very uncommon for women over 42 to conceive with their own eggs. We also routinely recommend assisted hatching for these patients as pregnancy rates have been shown to improve with this treatment.
During our discussions, we also advise women over 40 of the availability of IVF with an ovum donor and the excellent success rates that are realized with this kind of therapy (greater than 50 percent per treatment cycle). We realize that making a decision to choose ovum donation may not be an easy one and that many women will first want to try to conceive with their own eggs.
Polycystic Ovarian Syndrome (PCOS)
I have irregular menstrual cycles, and my doctor told me I have polycystic ovary syndrome. What does this mean?
Polycystic ovary syndrome (PCOS) is one of the most common causes of infrequent ovulation and irregular cycles in women. The exact cause is as yet unknown and in some cases may be genetic. In this syndrome, the ovaries produce an excess of androgens (male-type hormones) that prevent the egg from maturing normally, and the ovaries often have a multicystic appearance on ultrasound (hence the term polycystic ovaries) as a result of this arrest in maturation. Higher androgen production may also be associated with excess hair growth (hirsutism) on the face, chest, and abdomen. Because of fewer normal ovulations, women with PCOS often have difficulty conceiving. In addition, many patients with PCOS are resistant to the action of insulin and thus should be screened for diabetes.
Because ovulation is infrequent when PCOS is present, the uterine lining does not shed regularly. Women who don’t menstruate regularly are at increased risk for developing cancer of the lining of the uterus (endometrial cancer). This can be prevented by treatment with a medication known as Provera®, which will induce a menstrual flow. Provera® is a tablet taken daily for 12 to 14 days every two or three months.
If a woman with PCOS wishes to conceive, ovulation can usually be stimulated with a medication known as clomiphene citrate. If this treatment is unsuccessful, injectable medications, called gonadotropins, may be necessary. Gonadotropins are very successful in inducing ovulation, though they are more often associated with multiple pregnancies than is clomiphene citrate.
Another treatment that has helped some patients is surgical “drilling” of the ovaries. This laparoscopic procedure temporarily reduces androgen production by the ovaries and may result in spontaneous ovulation or may improve the response of the ovaries to ovulation inducing medications.
What is hysterosalpingography (HSG)?
The HSG is an outpatient procedure performed in a radiology center. A special iodine-containing dye is injected through the cervix. It flows into the uterine cavity and through the fallopian tubes. If the tubes are not blocked, the dye will spill out of the tubes and into the abdomen, indicating that the tubes are open. X-ray images will be taken during the procedure to provide a permanent record of the condition of the tubes and the uterine cavity. The actual progress of the dye flowing through the tubes can be followed on a fluoroscopy TV monitor. The X-ray images are available in a few minutes and can be examined by the radiologist, the gynecologist, and the patient. HSG is optimally performed within the first 11 days of a normal menstrual period.
To undergo an HSG, the patient first lies flat on the X-ray table. A vaginal speculum is then inserted (as in a Pap smear). The cervix is usually grasped with a holding instrument, and a small cannula is inserted into the cervical canal. The liquid dye is then injected, and X-ray images are taken. The patient may be instructed to turn from side to side to provide the best visualization of the pelvic organs.
Why is hysterosalpingography performed?
An HSG may be recommended in cases of infertility in order to diagnose a blockage of one or both tubes that may prevent union of the sperm and egg. In addition, because this procedure provides an image of the outline of the uterine cavity, it may help in detecting abnormalities of the uterus that could cause infertility, repeated miscarriages, or abnormal vaginal bleeding. The HSG procedure is sometimes performed before tubal ligation reversal surgery in order to show the lengths of the remaining tubes.
Is the procedure uncomfortable?
After injection of the dye, the uterus may respond by having cramp-like contractions. By taking 800 mg of ibuprofen (such as in Motrin® or Advil®) one hour prior to the procedure, most patients avoid discomfort. If you cannot take ibuprofen or are especially anxious, your physician may prescribe other medications.
What are potential complications and side effects of HSG?
During insertion of the instruments and injection of the dye, there will likely be cramping and discomfort, which usually disappears after a few minutes. A small percentage of patients may experience more prolonged discomfort, especially if the tubes are blocked and the liquid dye is unable to flow out of the uterus promptly.
A small percentage of patients may develop infection of the uterus, tubes, or pelvis following this procedure. This is more common when the tubes have been damaged previously by infection or other causes. Infection in the tubes can lead to infertility, but the risk of infection after an HSG is low (estimated at 1 percent). Some patients will be placed on antibiotics before the procedure in an effort to prevent infection. If your HSG shows blockage of the tubes and you have not taken antibiotics before the procedure, you may be given an antibiotic prescription for use after the HSG.
Allergic reactions are possible after injection of the iodine-based dye. During the procedure, a small amount of X-ray irradiation will be directed into the pelvic area and ovaries. The procedure is scheduled early in the cycle to prevent irradiation of an early pregnancy.
What are the alternatives to HSG?
In some cases, a saline-infusion ultrasound, MRI, laparoscopy, or hysteroscopy can also be used to provide information similar to that provided by HSG.
Should I use contraception during the cycle in which I have my HSG?
No, this is unnecessary unless you are uncomfortable not using contraception for some reason. There is some evidence in the medical literature that conception rates may be greater in cycles during which an HSG is performed.