IUI with Clomiphene, a First Line Treatment for Infertility


This information is provided for couples who may just be starting out in fertility treatments and are trying to conceive using IUI with clomiphene. CNY Fertility Centers provide infertility services including low cost IVF (In Vitro Fertilization) for couples who are starting or continuing their families in Albany, New York, Rochester New York and Syracuse, NY. In addition to our local services we work with patients from across the country and world offering affordable IVF and fertility treatments.

Unexplained infertility is when a couple can’t conceive although the woman is ovulating, and her fallopian tubes, uterus and partner’s semen results come back normal after testing. Some of the women have had endometriosis diagnosed and treated, thus are not truly unexplained, but do fit into this category in terms of an approach for treatment.

Clomiphene is inexpensive, and acts in women who already ovulate to stimulate production of several eggs during a treatment cycle. Clomiphene causes the brain to misinterpret blood estrogen levels. This induces the pituitary gland to produce a surge of the follicle stimulating hormone or FSH. The result is the production of more than usual numbers of follicles, each with one egg.  Intrauterine insemination (IUI) places more sperm into the uterus and then the fallopian tubes than could ever reach through intercourse. Thus more bullets are shooting at more targets.

The combined use of clomiphene and IUI has been shown to nearly double the results compared to using clomiphene alone to improve pregnancy likelihood (Guzick, 1998). The master student of IUI, Dr Richard Dickey and colleagues in 2002 compiled a large series in New Orleans and reported almost 10% success per cycle.

The distinguished Boston IVF group in a study led by Dr. Alan Penzias recently confirmed a cycle success rate of 11.5% (Dovey, 2008) from over 4000 cycles of treatment. The patients were ovulatory and some of the men had low sperm counts.  The success of treatments cumulatively over up to four cycles, was successful in 24% of patients under age 35. Age specific pregnancy rates per cycle ranges from 12% under age 35 to 4% over age 40. Corresponding decreases in overall success were seen according to age. Only one patient was successful (1.8%) of the 55 women treated over 43 years of age.

The study verified findings by others who found that 90% of success is found in three or four cycles. Those who are not pregnant by then should move to gonadotropin and IUI or IVF therapy.

At RBA in Atlanta, Dr Massey and colleagues found that the addition of a chemical called PAF to the sperm wash dramatically improved success rates (Roudebush 2004) to nearly double those without it. This is a reasonably simple method which more clinicians might use.

Those who are concerned with cost effective treatment for infertility continue to believe that clomiphene and IUI are a good treatment for younger patients who are trying to conceive, and fit the criteria outlined.

Selected References
Dovey S et al Fertil Steril 2008:90:2281-86
Guzick, DS et al Fertil Steril 1998;70:207-13
Dickey RP et al Fertil Steril 2002;78:1088-95
Roudebush WE et al Fertil Steril 2004;82:52-56


All About Injectables


Injectable medications are used for IVF or IUI cycles. One of the main processes in an IVF or IUI treatment cycle is the controlled stimulation of the ovaries, to produce eggs. The medications used in ovulation induction are called gonadotropins. Brand names include Follistim, Gonal-F, Menopur, Bravelle, and Repronex. Gonadotropins are primarily used to treat two types of women: 1) those who do not ovulate, ovulate irregularly, or have failed to conceive using Clomiphene citrate (Clomid) and 2) women who ovulate on their own, but may need help in producing multiple eggs, and whose bodies would benefit from the enhanced hormonal environment.
How do they work?
Gonadotropins are natural hormones that trigger the ovaries to make eggs. They are generally safe to use, but do require experience and careful monitoring.In a natural menstrual cycle without any medications, a woman produces one or two follicles, which are fluid filled sacs that contain an egg. The growth of the eggs and their release from the follicles are influenced by the secretion of two hormones from the pituitary gland: Follicle Stimulating Hormone (FSH); and Luteinizing Hormone (LH), both known as gonadotropins.When a woman becomes menopausal, her pituitary gland secretes large amounts of these hormones in an attempt to stimulate the ovaries, which no longer function. Gonadotropins (other than Follistim and Gonal F) are manufactured by extracting FSH and LH from the urine of post-menopausal women. Menopur contains both FSH and LH, while Bravelle contains only FSH.For a woman going through infertility treatments, these extracts must be injected and cannot be taken orally, because they would be digested by the stomach.Recently, gonadotropins (Gonal-F, Follistim) have been manufactured in the laboratory using recombinant technology, which allows a pure form of FSH to be produced. This is not a human tissue or urinary by-product, it is a recombinant FSH. Since it is more pure, it may be self-injected, using a small needle just under the skin.


Male Factor Infertility


One of the contributing factors to a couple’s fertility difficulties can be problems with sperm number or function. Approximately 15-20% of infertility can be ascribed to male factor infertility. When sperm are evaluated, they are assessed for quantity, motility, and how normal they look. Results can appear normal, borderline, or severely abnormal. Severely abnormal semen analyses will often require in vitro fertilization with intracytoplasmic sperm injection (IVF-ICSI) to achieve pregnancy. Normal or borderline sperm may be able to generate a pregnancy, but at a reduced chance of success.
An important item to remember is that a semen analysis does not measure male fertility; it measures sperm production. From those numbers, we try to draw connections between analyses and chances of pregnancy, but the correlation is not always exact. If problems with sperm production are identified, urological evaluation may be suggested. A urologist can perform a focused history, physical exam, and laboratory assessment, that might identify a reason behind the male’s difficulties. Many times, a hormonal or anatomic reason can be identified, which might be treated with medication or surgery.
Treatment for male factor generally involves increasing the number of normal, motile sperm having access to the eggs. This can be done with timed intercourse around the time of ovulation, intrauterine insemination, or IVF-ICSI. With intrauterine insemination, the seminal fluid is exchanged with neutral, hypoallergenic media, and the best-swimming sperm are collected after treatment in a centrifuge. Misshapen, immotile sperm are discarded, and the fraction of strong-swimming sperm is placed with a thin catheter into the woman’s uterus. Conception will still rely on the sperm’s ability to reach the egg, bind to its shell, and fertilize. If an insemination does not work, there is no way to tell where the process failed.IVF with ICSI minimizes failure by leaving the least to chance. Individual normal, motile sperm are carefully placed into oocytes, giving the highest chance for fertilization. The fertilized eggs are placed directly into the uterine cavity, minimizing the chance for ectopic pregnancy.
Other recommendations for maximizing male fertility include eating a regular diet, and avoiding tobacco, alcohol, and illegal drugs. One multivitamin per day may also help. The elements most likely to impair sperm number or quality include chemotherapy, radiation therapy, and anabolic (muscle-building) steroids. Many times, male infertility can not be “fixed”, but its effects can be minimized with intrauterine insemination or in vitro fertilization.


Sperm Washing


Sperm washing is performed on semen samples that will be used for Intrauterine Insemination (IUI), In Vitro Fertilization (IVF) or IVF with Intracytoplasmic Sperm Injection (ICSI). The sperm washing process facilitates the segregation of motile sperm from immotile sperm, dead sperm and seminal fluid.
Procedures requiring sperm washing
Sperm washing is important for patients planning to have an IUI. During natural conception, the vagina and cervix act as automatic ‘sperm washers,’ removing seminal fluids containing prostaglandins, which can cause cramping in the uterus. After sperm washing, the isolated motile sperm are placed directly into the uterus, bypassing the vagina and cervix, bringing the sperm into close proximity to the fallopian tubes, where eggs are fertilized.
Sperm washing is used to prepare semen samples for IVF and IVF with ICSI as well. The separation of motile sperm allows the embryologist to add the motile sperm into a petri dish, containing eggs for IVF. To fertilize eggs for patients using IVF with ICSI, each sperm is individually selected using a micro tool on a powerful microscope, and then directly injected into an egg. Removing unnecessary debris from a semen sample allows the embryologist to pick sperm easily, without clogging the micro tool.
The sperm washing process
After a semen sample is collected, the andrologist allows it to liquefy for approximately 20 minutes on a warmer. The sample is then assessed for sperm count, motility, progression, volume and viscosity. Once all the parameters are determined, the semen is placed in a test tube, on top of two liquids with different densities (called a “gradient”), which will act as a filtering system.
The gradients contain silane-coated silica particles in a specific concentration. The top gradient is less concentrated than the lower gradient. The semen and gradients are then centrifuged, causing the seminal fluid to be trapped in the top layer, non-motile sperm in the middle layer, and motile sperm in a pellet at the bottom. The pellet of motile sperm is re-suspended in another liquid media, and the concentration, motility and progression of the sperm are evaluated. The sample is then ready for IUI, IVF or IVF with ICSI.