Female Infertility Diagnosis: Plumbing Problems

September 29, 2010Carole 1 Comment »

In part two of female infertility diagnosis, I thought I’d put on my plumber’s hat- well, sort-of- and talk about the glorious female reproductive tract – the plumbing that gets the egg to sperm and the embryo to the uterus for implantation and pregnancy. When dear Mrs. Cannon taught our 7th grade sex education class (back when kids still learned about sex in school), she  introduced us to the female reproductive system by drawing what looked like a bad picture of a cow’s head on the chalk board. It came complete with the long face in front (vagina plus uterus) and the curled ears (or horns?) sticking out from the side (the fallopian tubes with ovaries hanging off them).

Okay, I never said our sex education was good, just available. She never really used the right names for the parts of the tract so it took a while for us to catch on that it really wasn’t about cows at all. So started my lifelong obsession with reproduction and may explain the five years I spent doing reproductive research with cows at Penn State, but I digress. Here’s a better drawing of Mrs. Cannon’s cow head.

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Every woman should know- and teach her children-  how the reproductive system works because everybody should know how they came to exist, just as a matter of principle.

The Fallopian tubes. The Fallopian tubes are amazing because they not only collect the eggs from the surface of the ovary but they provide a hook-up spot for eggs and sperm that is simply perfect for fertilization. Then, as if that wasn’t enough, they provide the early nursery for the new embryo for the first five days of its life, while gently transporting it to the waiting uterus for implantation. Talk about doing it all. The Fallopian tubes perform this magic in a structure a scant five inches long.

Gabriele Falloppio (also spelled Falloppia), a 16th-century (c. 1523-62) Italian physician and surgeon gave one of the earliest and best descriptions of the anatomy of the human oviduct and his name still remains associated with the human oviduct today. The ends of the tubes have long fimbria, these feathered ends that sweep over the ovary at ovulation, sweeping up any eggs and pushing them into the tube. The inside of the Fallopian tubes are lined with cells sporting hairy projections called cilia which wave like a tiny field of wheat to carry the egg and then embryo along the tubes toward the uterus.

Damage to these ciliated cells or blockage of the tubes caused by infection or traumatic scarring can block this normal movement to the uterus and cause an ectopic pregnancy. An ectopic pregnancy simply means a pregnancy outside the uterus, usually in the tubes but other unusual sites (such as ovary, cervix and other intra-abdominal sites)  have been reported. Some studies suggested that smoking may also interfere with the proper movement of these cilia, preventing egg-pick up at the ovary end and egg/embryo transport in the tube, resulting in failed implantation or ectopic pregnancy.

The Fallopian tube as embryonic nursery. The tubal environment has been perfected over millions of years of evolution to provide the perfect nutritional and hormonal environment for the growing embryo. Hormonally regulated secretions produced by the fallopian tube change throughout the cycle as the needs of the egg and later embryo change. In fact, the profile of secreted proteins is actually different in the three different structural regions of the tube, the infundibulum containing fimbria end (the feathery egg-picking up end), the middle section called the ampulla and the skinny section that attaches to the uterus called the isthmus.

In cattle, there is an estrus-associated protein which is secreted into the tubes only around the time of heat (or estrus) when sperm are likely to enter the tubes looking for an egg. This estrus-associated protein becomes associated with both eggs and sperm and was found to be critical for successful fertilization. Similar proteins have been found in other domestic species and primates, including humans. You can read a review on the biological function of these ovulation induced proteins in various species. Investigation into the function of these proteins is still on-going but could lead to a better understanding of idiopathic ( or unknown causes) of infertility in patients. It is not far-fetched to imagine that problems with the secretion or function of these critical molecules may account for some cases of idiopathic infertility that are successfully treated by IVF.

Swollen fluid-filled tubes called hydrosalpinx. Sometimes the Fallopian tubes become blocked and excess fluid accumulates causing the tubes to swell up like balloons. These hydrosalpinx disrupt normal function, making fertilization and pregnancy through intercourse (or IUI) impossible. The presence of large hydrosalpinx are also associated with a reduced success rate with IVF. Reproductive Endocrinologists (REs) sometimes recommend removal of the swollen tube (salpingectomy)  or tubal ligation before attempting IVF because IVF pregnancy rates are higher in the absence of these abnormal structures.Why do hydrosalpinx interfere with IVF success? it is not clear but several possibilities have been suggested. The leaking fluid may wash out any embryos attempting to implant. The leaking fluid may be embryo toxic or simply filled with debris that interferes with implantation and embryo development when it enters the uterus.

Open tubes are necessary for intercourse or intrauterine insemination (IUI) to result in pregnancy. Because fertilization happens in the tubes after intercourse or IUI, it is critical that these tubes be unblocked and healthy. Some couples endure countless rounds of Clomid and intercourse or Clomid and IUIs  (or injection medications and IUI/intercourse) without knowing if they have sperm (no semen analysis was performed) or an open tube to work with (no one looked at the tubes). Especially if you are using injection medications, you may easily find yourself spending a third of what an IVF costs only to find out too late that these “cheaper” IUIs were doomed to failure because the diagnostic work up was insufficient to diagnose blocked tubes (or azoospermia- no sperm). Don’t let this happen to you. Sometimes it saves money, time and emotional stress to do a thorough diagnostic workup on the front end, instead of the middle of treatment.

The uterus as Grand Central Station.  The uterus is a very special site housed between the vagina and the Fallopian tubes. Sperm travel through the vagina, cervix and uterus to get to the Fallopian tubes and find the egg. Ever wonder how long it takes a sperm to swim to the Fallopian tube? Check out this chart for different species. Human sperm has been clocked in at 5 minutes to one hour. Once the sperm arrive in the tubes, they hang around for 24-48 hours, waiting for an egg to arrive. The eggs shelf-life is less, approximately 24 hours so the best strategy for pregnancy is to have some sperm hanging around waiting for an egg. That is why doctors advise patients to have intercourse approximately every other day to optimize sperm number and location. Anyhow, once the embryo is created, it heads to the uterus for implantation, carried along by the waving cilia lining the tube.  (Can’t you just see the embryo crowd-surfing the cilia to the uterus??) The embryo’s trip through the tubes to the uterus takes about five days.

The amazing elastic incubator. The uterus is a muscular organ which is only a few inches long when not pregnant and can expand to twelve inches or more in size when fully pregnant.. The uterus is composed of various layers including an upper uterine lining or endometrium which is replaced monthly at menstruation.  The endometrium is where the hatching blastocyst stage embryo “docks” with receptors on the cellular surface  of the endometrium to begin the implantation process. Deeper muscular uterine layers  grow in size with the pregnancy and provide tremendous contractions to expel the baby at delivery. After the baby is born, the uterus returns to its compact pre-pregnancy size (or nearly).

Did you know that there are molecular processes that actually stop the embryo from implanting too far into the deeper layers of the uterus? Rarely, these safety mechanisms fail. If the embryo is not stopped, the relentless implantation program continues and the embryo develops into a tumor instead of a baby. In “How an embryo is like a tumor“,you’ll find a brief comparison of how the molecular mechanisms that allow the invasive march of the embryo into the uterine layers for implantation may also be exploited by tumor cells when they metastasize and invade other tissues. Gestational trophoblast disease is an umbrella term for four types of rare conditions when the embryo goes rogue resulting in benign or malignant tumors. They include hydatidiform mole (complete or partial), invasive mole, choriocarcinoma and  placental site trophoblastic tumor.

Uterine Fibroids. Uterine fibroids are a kind of tumor, almost always benign (non-cancerous), which can grow in different layers of the uterus and range in size from apple seed sized to larger than grapefruits. They may be small and numerous or large and few or anything in between. They may cause no noticeable problem for the patient or they may cause all kinds of bleeding problems and abdominal discomfort. Depending on their size and location, they have the potential to prevent embryo implantation or cause pregnancy loss. Depending on their size and location, you RE may recommend that they be removed surgically (myomectomy) before initiating fertility treatment. Sometimes gonadotropin releasing hormone agonists such as Lupron are prescribed to medically shrink the fibroid(s) before the start of infertility treatments or even before surgery to remove the fibroids. Other surgical methods to remove fibroids such as laser surgery or MRI-guided ultrasound surgery are being developed but are not widespread yet and may be considered experimental by your insurance company (meaning they will balk at paying).

Looking at the Fallopian tubes and uterine cavity. A basic diagnostic test for female fertility is to determine whether the tubes and uterine cavity are open for business. There are several ways to get a look at your tubes and uterus including hysterosalpingography, or sono-hysterosalpingography. These links will take you to a more detailed patient oriented explanation of these tests. The traditional hysterosalpingogram (HSG)  requires that a contrast dye be injected into the uterine cavity and tubes until it spills out the tube end and an X-ray image is taken. The more recent sono- HSG uses saline injection and ultrasound of the fluid filled cavities to visualize the uterine cavity and tubes. Surgery (laproscopy) to introduce tiny cameras into the pelvic cavity can also be used to directly look at the outside of your tubes and uterus for the presence of endometriosis, pelvic adhesions or other macroscopic problems.

Understanding the biology of reproduction is the first step to taking charge of your infertility treatments, starting with a good diagnostic work-up. I hope this journey through the female reproductive tract has given you  some background information for better discussions with your doctor about your diagnosis and treatment plan.

© 2010 – 2011, Carole. All rights reserved.

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