Clomiphene Citrate (Clomid) has been in clinical use since 1957. Clomid is the most commonly used oral fertility medication for inducing ovulation. If a pregnancy is going to occur, over 90% of the Clomid pregnancies with timed intercourse (or insemination) will usually happen within the first 3 to 4 cycles (Monthly pregnancy rates 10-15%). Almost all OB/Gyns will refer their patients to a reproductive endocrinologist for more advanced treatments after 3 or 4 failed Clomid/ intercourse attempts.
Clomid (an anti-estrogen) stimulates the pituitary gland to produce more follicle stimulating hormone (FSH) which causes the ovary to usually develop one or two mature follicles (egg sacs), each containing an egg. Clomid tablets have a positive effect on the ovaries (increased eggs and increased progesterone). However, Clomid's anti-estrogenic effects on the cervical mucus quality and on the uterine lining are unfavorable over time. That's why most pregnancies with Clomid and timed intercourse happen within the first 4 tries and rarely after that. Eventually the cervical mucus becomes unfavorable (less sperm picked up) … for every 1 million sperm deposited vaginally during intercourse probably only 1 sperm per million makes it to the fallopian tubes. In addition, as the uterine lining becomes thinner from Clomid, it becomes less suitable for an early embryo to implant.
If Clomid with intercourse does not result in a pregnancy, future appropriate options include trying Letrozole tablets instead or using Clomid in conjunction with intrauterine insemination (IUI), or FSH gonadotropin injections with or without Clomid along with inseminations and/or in vitro fertilization (IVF). Each option has its various benefits, pregnancy success rates, risks of multiples and variable costs. Your work schedule and your available time commitment may also be an important factor. Women under 40 with normal tubes (or 1 normal tube) and normal or slightly abnormal sperm are good candidates for trying Clomid with IUI for up to 3 or 4 attempts since this treatment plan is the least risky, least expensive and easiest regarding your time commitment. Clomid combined with IUI is more successful than with intercourse. If a successful pregnancy is going to occur with this treatment plan (Clomid/IUI) it usually happens within the first 3 or 4 tries. Therefore, if no success, it’s time to move on to other treatment options, such as in vitro fertilization (IVF).
During your menstrual period, on days 2, 3, 4 or 5, we check a baseline ultrasound to rule out ovarian cysts and make sure your ovaries are okay for stimulation. Then we will tell you which 5 days to take the Clomid tablets (variable doses), usually beginning on cycle days 3, 4 or 5. Often times we will add natural estrogen and/or natural progesterone to the therapy in order to counteract the antiestrogenic
effects of Clomid (de Ziegler protocol). Approximately 4-5 days after your last Clomid pill we will set up a follicle ultrasound since 95% of women are usually ready at that time with 1 or 2 ‘mature-sized’ follicles, approximately 18-20 mm in size or larger. If the follicle(s) is ready (18-20+ mm), we then give/order an injection of hCG (human chorionic gonadotropin), a pregnancy hormone which mimics the LH (luteinizing hormone) surge in nature. If there are 3 mature follicles, we recommend cancelling in order to avoid triplets. This hCG injection (Ovidrel; Novarel; Pregnyl) causes ovulation 24 to 38 hours later, allowing for excellent timing of the IUI. Do not have intercourse the night before your scheduled IUI. However, intercourse any time after the IUI is fine.
Intrauterine Insemination (IUI)
At FCI, we generally do IUIs 7 days a week. The husband/partner can collect his specimen at home in a sterile container we provide or use our collection rooms in each of our offices. The specimen should ideally get to us within one to two hours if collecting at home. If the female has to bring in the specimen from home, she will spend more time in the office waiting for the sperm to be prepared. If the man can bring it in or collect in the office, she will spend far less time in the office. When using frozen sperm (as with a sperm donor), it can be thawed right before IUI.
It takes approximately one hour to wash and process the sperm. Sperm washing is done
to separate out the sperm from the debris and chemicals in the semen that don't belong inside the uterus. Then a "swim up technique" is used to separate out the better swimmers to improve the motility of the specimen. Most IUIs are done by the fertility nurses under the direction of the doctor.
The actual IUI uses a thin, soft plastic catheter to deposit a few concentrated drops of millions of highly motile sperm into the top of the uterus. This IUI takes 1 to 2 minutes and is generally painless or very mildly uncomfortable. Thousands of motile sperm will make it to the fallopian tubes. Then we have you rest, lying down for 10 minutes in order to minimize uterine contractions. After that there are no restrictions in activity. Intercourse later that day or night is perfectly safe.
Most studies indicate that with Clomid therapy, one IUI per month is essentially as good as 2 but there are exceptions, such as when using frozen sperm. If the man’s sperm count is reasonable we may occasionally suggest 2 IUIs per month. We usually supplement with natural progesterone as needed. One week later, we check progesterone levels and then do a pregnancy test 2 weeks after the IUI.
Summary: IUI is very safe, simple, relatively inexpensive, and helps get far more sperm into the Fallopian tubes than intercourse. Ideally, we want only 1 or 2 mature-sized follicles (18+ mm) and if 3 mature-sized follicles are present, we will give the couple the option of canceling, as well as discussing selective reduction options. If 4 or more mature follicles are present, we will recommend cancellation. Risks and side effects include primarily multiple births (6-8% twins, less than 1% triplets, less than .1% quadruplets) with resulting premature births and rare ovarian hyper stimulation (OHSS). Remember, the risk of multiples does not increase with IUI since more sperm getting into the tubes is beneficial, whereas too many eggs being released, is not safe.
by Laurence A. Jacobs, M.D.