The Place of IntraUterine Insemination (IUI) in Infertility
Printer-friendly versionby Camille Sylvestre, MD, FRCSC
Summer 2007
Summer 2007
Infertility affects 10 to 15% of all couples. Over the past 50 years, the frequency of infertility has increased because of a rise in sexually transmitted diseases and a generalized delay in childbearing age. Traditionally, intrauterine insemination with or without ovulation induction has been the first line of treatment for couples suffering from infertility. The causes of sub-fertility will be reviewed, especially the difficult category of unexplained infertility. The investigation and management with the different options of treatment will be presented. Finally, the value of starting with intrauterine insemination before in vitro fertilization will be discussed.
Causes of sub-fertility
For conception to occur, many key events must take place. A mature egg must be released from the ovary, picked up by a fallopian tube and then fertilized in that tube by a sperm. The embryo produced has to be transported in the tube towards the uterine cavity and must implant into the uterine lining to develop. A couple who does not achieve pregnancy after one year of unprotected intercourse is said to be infertile or and any problems arising during those steps could be the cause.
Disorders of ovulation. Regular menstrual cycles strongly suggest that a woman is ovulating. Cycle lengths of roughly 26-34 days are usually ovulatory, especially if accompanied by mid-cycle pelvic pain and clear cervical discharge, as well as premenstrual symptoms such as bloating and breast tenderness. If a woman has menstrual cycles significantly longer than that interval, she probably is not ovulating or ovulating infrequently, and it is the cause in about 30% of the cases of subfertility. A large proportion will have polycystic ovaries (PCO) visualised on ultrasound scan. The other common causes are hormonal (prolactin or thyroid problems), extremes of weight, age-related ovarian dysfunction and premature menopause.
Tubal factor. A tubal and/or adhesive factor accounts for 35% of all infertility cases. Blockage of the fallopian tubes can be the result of past sexually transmitted disease or previous pelvic or abdominal surgery. Adhesions around the tubes can occur as the result of past pelvic surgery, or peritoneal disease such as endometriosis. The tubes might be open on hysterosalpingogram but egg retrieval by the tube itself and transport may be impaired. An anomaly in the uterus such as fibroids, polyps or septa may have to be repaired before treatment.
Male factor. Male factor is the sole cause of infertility in about 20% of couples and contributes to infertility in a further 30-40%1. Absence of sperm (azoospermia) can be caused by an obstruction (vasectomy) or genetic or hormonal disorders. Diminution in sperm count or motility may result from hormonal problems, retrograde ejaculation, varicocele, primary testicular problem or environmental factors. In many cases, no treatable cause of poor sperm quality can be found.
Investigation for infertility
Past medical and surgical history of both partners and a physical exam of the female patient are usually performed at the first visit. The basic investigation includes a screening test for chlamydia trachomatis and a hysterosalpingogram for tubal factor, a day 21 progesterone for ovulation, and a semen analysis for male factor. If the female patient is suspected to be anovulatory, hormonal testing (serum LH, FSH, oestradiol, TSH and prolactin) on day 2-5 of her menses is required. A transvaginal ultrasound performed on day 2-5 of the cycle completes the evaluation of the uterine and ovarian anatomy as well as the ovarian reserve by counting the number of follicles, which contain the eggs. Other examinations such as laparoscopy and hysteroscopy can be done to clarify abnormal basic examinations.
Diagnosis & management of unexplained infertility
Infertility is said to be unexplained when a couple fails to conceive and no definite cause can be diagnosed after a complete evaluation. The incidence has been reported to be around 10% of the couples. There are many other immunological tests that have been developed but their validity has not been clearly demonstrated and they should be used with caution.
Ovulation Induction
The causes of infertility suitable for ovulation induction are the hormonal causes (PCOS, hypothyroidism), multi-factorial sub-fertility and unexplained infertility. The causes not suitable for ovulation induction are premature menopause, and chromosomal abnormalities. Close to optimal body weight must be attained before the start of treatment.
Clomiphene citrate (Clomid®, Serophene®). First used in 1961 for anovulation, it blocks the estrogen receptors at the level of the pituitary gland, which increases the level of FSH and LH, producing more eggs in the ovaries. The dose is 50-150 mg by mouth daily for 5 days starting from day 2 to 5 of the menstrual cycle. The dose should be augmented by 50 mg until an ovulatory cycle occurs. There is no advantage of a dose in excess of 150 mg. Once an ovulatory cycle is achieved, it is recommended to repeat for a maximum of 3 cycles, as 75% of the pregnancies will occur in the first 3 cycles. Negative side effects of clomiphene citrate treatment are hot flushes, thin uterine lining (endometrium), and rarely visual disturbances. After a baseline ultrasound at the beginning of the cycle to ensure that there are no ovarian cysts, the growth of the follicles and the endometrium during the treatment are followed by serial ultrasounds. Basal body temperature charts or urinary LH testing can also track the ovulation.
Aromatase inhibitor (Letrozole). It is a relatively new treatment in ovulation induction and is presently not approved by Health Canada. Its major advantage over clomiphene citrate is that it has presumably no effect on the endometrium. The dose is 2.5-5 mg by mouth daily for 5 days starting from day 2 to 5 of the cycle. There is no significant side effect to that medication.
Gonadotrophin injections (Puregon®, Gonal F®, Repronex®). In older women or those with longer duration of infertility, gonadotrophins (injections of FSH and/or LH) are preferable to clomiphene or letrozole as first line therapy because it can induce the development of three or four large follicles (controlled ovarian stimulation), while oral medications will generally produce one or two follicles. There are several protocols in the literature and either daily injections starting on days 2 or 3, or alternate day injections from day 3 can be safely and effectively used. The majority of pregnancies occur in the first 3-4 cycles and the pregnancy rate is approximately 8% with gonadotrophins alone. This treatment must be followed by ultrasounds because the risk of multiple pregnancies is 20-25% and the risk of ovarian hyperstimulation syndrome is 1%.
Intrauterine insemination (IUI)
When the dominant follicle reaches 18 mm, hCG injection is given and IUI is performed the next day. The partner brings a sperm sample that morning which is washed and inseminated by a small catheter in the uterus through the cervix. This procedure places the sperm closer to the egg. IUI alone in couples with unexplained infertility doesn’t increase the pregnancy rate. However, when IUI is combined with clomiphene citrate it increases cycle fecundity two- to three-fold, and with gonadotrophins three- to five-fold over the baseline chance of pregnancy in this patient group.
When we are facing a diagnosis of infertility, we need to look for the three main reasons, which are ovulation, tubal problems or male factor. In couples with unexplained infertility, anovulation, mild tubal and male factors, ovulation induction and IUI should be offered first when the female partner is young and the duration of the infertility is short. Ovulation induction with clomiphene Citrate should be replaced with gonadotrophins in longer infertility. It should be used for a maximum of 6 cycles before moving to In Vitro Fertilisation. In patients in late 30’s and a long period of infertility, IVF should be offered quicker as second-line treatment.
Frequently Asked Questions About Intrauterine Insemination
What is an IUI and how is it done?
An IUI - intrauterine insemination - is performed by threading a very thin flexible catheter through the cervix and injecting washed sperm directly into the uterus. The whole process doesn't take very long - it usually only requires the insertion of a speculum and then the catheter, a process that maybe takes a couple of minutes.
Where is the sperm collected? How long before the IUI?
Usually the sample is collected through ejaculation into a sterile collection cup. Most clinics want the semen to be delivered within a half hour of ejaculation, so if one lives close enough the sample can be collected at home. If not, one has to make do with a room at the clinic.
There is a delay between when the semen sample is dropped off for washing and when it is inseminated. The amount of time depends on the washing technique used, which takes 30 minutes to two hours. In most cases, the IUI will be performed as soon as possible as soon after washing is completed.
When is the best timing for an IUI?
Ideally an IUI should be performed within 6 hours either side of ovulation — for male factor infertility some doctors believe after ovulation is better. If two IUIs are scheduled, they are usually spaced at least 12 hours apart between 24 and 48 hours after the hCG. Some reports show no increase in success rates with two IUIs, but others suggest it may increase success as much as 6 percent.
Some doctors will base timing of IUI on a natural LH surge. In that case, a single IUI at 36 hours is the norm, but doing them at 24 hours is also pretty common since ovulation may be a bit earlier. When two inseminations are planned, they are usually timed between 12 and 48 hours after the surge is detected.
The egg is only viable for a maximum of 24 hours after it is released.
What is the success rate for IUI?
Searching through about a dozen medical journal articles and a number of web sites resulted in a rather wide range of statistics. Basically the odds of success are reported to be just under 6 percent and as high as 26 percent per cycle. The low statistics are with one follicle, while multiple follicles resulted in as high 26 percent success. Another influencing factor is sperm count. Higher sperm counts increase the odds of success; however, there was little difference between success with good-average counts and those with high counts. The overall success rate seems to be between 15-20 percent per cycle. The rate of multiple gestation pregnancies is 23-30 percent.
What does an IUI feel like?
Most women consider IUI to be fairly painless -- along the same lines as having a pap smear. There can be some cramping afterward, but often what is felt is ovulation-related rather than from the IUI. The catheter usually doesn't feel like much since the cervix is already slightly open for ovulation -- a poorly timed IUI might cause more discomfort at the cervix.
How long does washed sperm live?
Current research indicates that washed sperm can live 24-72 hours; however, it does lose potency after 24 hours. Another issue with IUI is that the sperm can keep on swimming beyond the fallopian tube, so the ideal window is really within 6-12 hours of the egg being released. Sperm can live up to 5 days in fertile mucus, 2-3 days being pretty common, so combining IUI with intercourse may provide better coverage.
Do I have to lay down after an IUI?
You don't have to lay down because the cervix doesn't remain open, but most doctors let patients lay down on the table for 15-30 minutes after the procedure.
Do I need to take it easy after an IUI?
Most people don't need to, but if you had cramping or don't feel well afterward it makes sense to take it easy for awhile. Some people reduce their aerobic activity and heavy lifting during the luteal phase in hopes it will increase the chance of implantation. It is more important to take it easy for a bit after IVF, as that is a more invasive process.
How long before an IUI should the male abstain from intercourse/ejaculating and store up sperm?
This depends on your individual situation, but it usually should not be more than 72 hours since his last ejaculation in order to ensure the best motility and morphology. Your doctor will likely give you more precise directives when necessary.
How soon after an IUI can I have intercourse?
Usually you can have intercourse anytime after an IUI . . . in fact, most doctors suggest having intercourse, when that is an option, soon after the last IUI to help make sure ovulation is covered. Your doctor may suggest waiting 48 hours to resume relations if you had any bleeding during the IUI.
Can the sperm fall out?
Once the sperm is injected into the uterus, it does not fall out. There can, however, be increased wetness after the procedure because of the catheter loosening mucus in the cervix and allowing it to flow out. Some doctors will insert a cup around the cervix to prevent leakage, but most do not.
How come I feel wetter after the IUI, like the sperm is falling out?
The catheter loosens cervical mucus and lets it come out more easily. It is common to see more fertile mucus after an IUI for this reason, as well as the fact that well-timed IUI should be close to ovulation.
How many follicles give my best chance of getting pregnant?
According to different studies, either 3-4 follicles gives one the best chance of getting pregnant, while more follicles beyond that simply increases the risk of multiples.
Does IUI make sense when there isn't a sperm count problem?
IUI can help on Clomid cycles where cervical mucus is a problem, and IUI increases the chance of success on injectable cycles no matter what the sperm count. It does make sense to try IUI if you can and haven't had success with intercourse. It is important to note that with intercourse, only the best and strongest sperm make it through the cervical mucus and up into the uterus and fallopian tubes. With IUI, more sperm will be available for fertilization.
How high a sperm count is needed for IUI?
A count above one million washed appears necessary for success.
How many IUIs should I try before moving on to IVF?
It depends on what you can afford and what meds you are doing. One might do 3-4 IUIs on Clomid before moving on to injectables, then do 3-4 cycles on injectables. If one doesn't have success after four good ovulatory cycles on injectables with well-timed IUI, it would be time to consider IVF.
Can IUI be done at home?
An IUI shouldn't be done at home without medical supervision because the sperm needs to be washed to prevent infection and cramps due to the prostaglandins in the semen.
Is bleeding common after an IUI?
It doesn't usually happen, but it isn't uncommon. It is most common to have some bleeding if the doctor had trouble reaching the cervix. Some women also have light bleeding with ovulation.
How long after IUI should implantation occur?
A: Implantation generally takes place 6-12 days after ovulation — so 6-12 days after a well-timed IUI.
How much does IUI cost?
This is definitely something to consult your doctor or clinic about as the price varies considerably. Ask for a rate sheet, if available, and also ask what your cycle is likely to entail.
What are the risks involved in IUI?
The main risks are some discomfort such as cramping and minor injury to the cervix that leads to bleeding or spotting. There are also risks of hyperstimulation associated with the use of ovulation induction medications such as clomiphene citrate (low risk) and gonadotropin therapy (higher risk). Proper technique and adequate monitoring reduce risks.
Can I take pain medications before or after the procedure?
Most women don't need medication for pain associated with IUI. If there is cramping, it is best to avoid medications such as ibuprofen and naproxen (NSAIDS), but Tylenol is considered safe (but maybe not that helpful for cramps).
What does "sperm washing" mean?
It is sometimes also called sperm preparation or spinning. It is a laboratory technique for separating sperm from semen, and separating motile sperm from non-motile sperm, for use in assisted reproduction (IUI, IVF).
How soon after an IUI can I go swimming?
Since the vagina doesn't open unless something pushes it, it is OK to swim shortly after your IUI . . . but because of how much one has invested in getting pregnant, it probably makes sense to wait 48 hours after your IUIs to go swimming.
About the author
Camille Sylvestre is Assistant Professor at the Department of Obstetrics & Gynecology of the McGill Reproductive Centre, McGill University, Montreal, Canada.