Tuesday, January 28, 2014

Treatment of Vaginal Agenesis using the McIndoe Procedure (in English)

The treatment of vaginal agenesis

There are two options for the treatment of vaginal agenesis:
Nonsurgical – Vaginal dilators are used (and this is the first option in the majority of cases)
Surgical – The McIndoe technique is the surgical procedure most commonly used in present day.

The McIndoe technique

… consists of performing a careful dissection between the bladder and rectum, thus producing a cavity which will be formed by inserting a vaginal mold covered with a skin graft.

For this operation, a split-thickness skin graft is used.

To obtain a split-thickness skin graft, the superficial layer of the skin (epidermis) along with a part of the underlying tissue (dermis) is used. The donor site can be any area of the body, but in the majority of the cases it is an area that can be hidden with clothing, such as the buttocks or the interior thigh.

The dermatome

A dermatome is employed to obtain a split-thickness skin graft. The dermatome powered by air or electricity is preferred due to the uniformity and size of the graft produced with this instrument.

(we see in this slide) The donor site

Once the graft is taken, a compress containing petroleum jelly is applied to the donor site and covered with a bandage.

The vaginal mold

… is constructed using a foam rubber covered by a condom. The graft is applied with the outer (epidermal) layer next to the vaginal mold. The graft is folded over the mold and sutured with interrupted stitches of synthetic absorbable 4-0 suture.

Dissection of the vaginal canal

Dissection of the vaginal canal is begun with a curved incision of the mucosa of the vaginal introitus.

(following slide)

The dissection is continued following a cleavage plane between the bladder and rectum towards the peritoneum, being careful not to injure the bladder or rectum. A gentle blunt dissection is all that is necessary to create an adequate cavity.

(The mold is inserted into the cavity)

The mold covered with the skin graft is inserted into the cavity. A sagittal view of the pelvis shows the form inserted into the new vaginal canal.

(Maintaining the mold in place)

To maintain the mold in place, the labia majora are sutured in the midline with interrupted sutures of 0-nylon without tension. The sutures are cut and the form removed for cleaning after 7 days.

Postoperative treatment

Initially, the patient keeps the mold in place during the day and night. After four weeks, she can attempt sexual intercourse. The patient continues to use the mold at night for about three months.

Tuesday, January 21, 2014

Treatment of Vaginal Agenesis using the McIndoe Procedure (en Español)

This is from a recent presentation I gave about my experience with the McIndoe procedure for the treatment of vaginal agenesis. The link is to a YouTube version of the Powerpoint presentation, and the text that follows is a narration of the slides. (I'll post the English version when I get a chance).


Corrección quirúrgica de la agenesia vaginal
Michael P. Steinkampf, MD

(El tratamiento de la agenesia vaginal)

Para el tratamiento de la agenesia vaginal, hay dos opciones:
No quirúrgico – se usa dilatadores vaginales (es la primera elección en la mayoría de los casos)
Quirúrgico – la técnica de McIndoe es el procedimiento quirúrgico más utilizado en la actualidad.

La técnica de McIndoe…

… consiste en realizar una cuidadosa disección entre vejiga y recto, formando así una cavidad, en la cual, acto seguido, se inserta un "molde" vaginal, recubierto con injertos cutáneos.

Se usa en esta operación El injerto de piel de grosor parcial

Para obtener un injerto de piel de grosor parcial, se utiliza la capa más superficial de la piel (epidermis) junto con una parte de la siguiente capa (dermis). El sitio donante puede ser cualquier área del cuerpo. En la mayoría de las veces es un área que se pueda ocultar con la ropa como los glúteos o la parte interior del muslo.

El dermatoma

Se emplea el dermatoma para obtener un injerto de piel de grosor parcial. El dermatoma accionado por aire o electricidad se prefiere debido al grosor uniforme y el tamaño del injerto producido.

(vemos en esta diapositiva) El sitio donante

Una vez tomado el injerto, se le coloca a la paciente, sobre el área donante, una compresa que contiene vaselina, cubierta con vendaje.

El molde vaginal …

… se construye utilizando un condón relleno de gomaespuma.  La forma vaginal se coloca en el lado epidérmico del injerto de piel de grosor. El injerto se pliega sobre la forma vaginal y se sutura a lo largo de su costura interrumpido con 4-0 sutura absorbible sintética. El exceso de injerto se recorta.

La disección del canal vaginal

La disección del canal vaginal se inicia con una incisión curva a nivel del borde mucocutáneo entre el introito vaginal y el periné.

(siguiente diapositiva)

Se continúa con una disección cortante inicial, que se cambia a disección digital, siguiendo el plano de clivaje del espacio virtual vésico-rectal hasta el peritoneo, teniendo mucho cuidado de no lesionar la vejiga y el recto. La disección roma suave es todo lo que se necesita para crear una cavidad adecuada.

(El molde se inserta en la cavidad)

El molde de la piel cubierta se inserta en la cavidad. Una vista sagital de la pelvis muestra la forma de la piel cubierta de insertarse en el nuevo canal vaginal.

(Mantener el molde)

Para mantener el molde en su lugar, los labios mayores se suturan en la línea media con interrumpidas 0 suturas de nylon sin tensión. Se extrae la forma para limpiar después de 7 días.

El tratamiento posoperatorio

Inicialmente, la paciente mantiene el molde en su lugar durante el día y la noche.
Después de cuatro semanas, ella puede tener una vida sexual.
La paciente continúa con el uso del molde en forma nocturna por tres meses.

Muchas gracias por su atención.

Thursday, January 24, 2013

Treatment of Vaginal Agenesis - Part 1

Most of the patients I see have fertility problems, usually infertility or recurrent miscarriages, but I have always been interested in the treatment of birth defects of the female reproductive tract, even if they are unrelated to fertility. One such problem is vaginal agenesis.

About 1 of every 5000 women are born without a vagina. This syndrome is sometimes called MRKH (Mayer-Rokitansky-Kuster-Hauser Syndrome, named after some of the people who first described the condition). Women with vaginal agenesis have normal ovaries (and fallopian tubes), but in most cases the uterus is very small or absent. They go through puberty like any other women, but of course they never menstruate. Most of the time, the diagnosis is first considered around age 16. If you encounter a girl who has not yet menstruated two years after having breast development, this is one diagnosis to consider.

The cause of vaginal agenesis is not known, but there is probably some genetic factor involved, as women with this disorder sometimes have a family history of similar problems. I published a paper years ago about identical twins, one with vaginal agenesis, and the other with a normal vagina but virtual absence of the lower leg bones (go here to read the abstract of that paper: http://www.ncbi.nlm.nih.gov/pubmed/12969715). That case was a dramatic example of the relationship between the development of the genital tract and the skeleton. Women with vaginal agenesis may also renal (kidney) and hearing problems.

Diagnosis of vaginal agenesis

Usually, vaginal agenesis is diagnosed by a history and physical exam. I also do a pelvic ultrasound to look for other pelvic abnormalities, and I check to see that both kidneys are present. If there is some question about the diagnosis, a pelvic MRI, a chromosome test, and hormone tests might also be obtained. There are some other conditions that can mimic vaginal agenesis (like androgen insensitivity, a transverse vaginal septum, and an imperforate hymen), so if this disorder is being considered, it’s important to find a doctor who is experienced in making the right diagnosis rather than just someone who can help the patient make a vagina. I have to admit that many reproductive endocrinologists are so interested in doing fertility treatments like in vitro fertilization that they don’t have much interest in (or experience with) this problem, so if you live somewhere far from me, you may have to search around to find someone with expertise in dealing with vaginal agenesis. Often that will be at an academic medical center, but that isn’t true where I live.
Here is what vaginal agenesis looks like (the catheter is in the urethra):


Management of vaginal agenesis
So, what do you do if your doctor has said you have vaginal agenesis? Of course, you need to learn all you can about the condition. A good place to start is a Web site put up by Boston Children’s Hospital (http://www.youngwomenshealth.org/mrkh_teen.html). I'm sure other sources of information exist, but that is the best one I have found. Then, if you live not too far from Birmingham, Alabama, you should come talk to me. We’ll do some tests to confirm the diagnosis (and look for related issues that might need treatment, like a functioning uterine remnant) and talk about how to fix your problem.

Of course, you don’t have to do anything at all about vaginal agenesis. I saw a young couple many years ago that presented with infertility - they didn’t realize the wife was born without a vagina! It was clear from her exam they were engaging in anal intercourse (and they refused any treatment.) I have also seen one couple who had managed to dilate the woman’s urethra by repeated attempts at intercourse. I can’t say that I recommend either of these options. Basically, there are two ways to treat vaginal agenesis: use of vaginal dilators, or surgical treatment.

Vaginal dilators are used to slowly create an opening where the vagina should be. This is done by the woman pressing a dilator into the vaginal orifice 15-20 minutes at a session twice a day. It usually takes 3 to 6 months to get a functional vagina. The advantage of this technique is that surgery isn’t needed; the disadvantage is that it takes a long time, and it doesn’t always work. There have also been some reported cases of vaginal prolapse (meaning the vagina turns inside out and falls outside the body) among women who have used dilators to create a vagina. I think it is always best to try vaginal dilators first, since even if it doesn’t work, it can sometimes make the surgery a bit easier. If you read through the Web site I listed above, you may surmise that whoever wrote the material is a strong proponent of vaginal dilation, even if it takes over a year to get results. I am less enthusiastic, and if someone comes and says “no dilators, let’s do the surgery”, I’m OK with that; maybe it’s because I’ve had good results with surgical treatment, and because I sympathize with women who don’t want to work for over a year to get a functional vagina. (The twin whose case I published was having intercourse with her newlywed husband six weeks after surgery.)

There are several surgical options to make a vagina: using a split thickness skin graft (the McIndoe procedure), using a loop of small or large intestine, or using a surgically implanted device that provides a constant tension on the vaginal orifice (the Vecchetti procedure). You can use a full-thickness skin graft or a flap of tissue freed up from the upper thigh, but I think this is seldom done, in part because you get hair follicles growing in the vagina. I think that using a loop of bowel has fallen out of favor, too, since it is major surgery that requires cutting a loop of intestine. Also, women who have this procedure are said to have a chronic vaginal discharge from the intestinal segment that requires a sanitary pad to control. I have only seen one patient who had a vagina created from a loop of bowel, and I was unimpressed with the result. The vagina was very short (less than one inch deep); there didn’t seem to be a bothersome discharge, though, and the couple didn’t complain about the outcome, so I guess it was OK for them.

The Vecchetti procedure is a fairly recent development from Europe. It requires laparoscopy to insert sutures that connect a special tensioning insturment mounted on the abdomen to a plastic olive-shaped device installed at the vaginal orifice.The patient typically stays in hospital for 7 to 10 days and then undergoes another surgical procedure to remove the device. This technique is sort of a ramped-up dilator procedure. The outcomes are supposed to be good, but since the procedure is still fairly new, we don’t know as much about the long-term results as some of the other options, and it does involve some surgery. A few years ago I observed several Vecchetti procedures, but in the end I didn’t think it offered an advantage over what I currently do, which is the McIndoe procedure.

Next post: How to make a vagina using the McIndoe procedure.

Thursday, November 15, 2012

Birth Defects and Fertility Treatment - Good News or Bad?

Many infertile patients are rightfully concerned that the risk of birth defects might be increased among children conceived using fertility treatments, especially in vitro fertilization (IVF). Here are the titles of the first five articles that popped up when I did a Google search yesterday using "fertility treatment birth defect" as the search terms:

"Common fertility treatments raise birth defect risk, study finds"
"Birth-Defect Risk Higher With Fertility Treatments, Study Shows"
"Infertility Treatments May Raise Birth Defect Risk"
"Fertility Treatments May Raise Risk for Birth Defects: Study"

Bad news? Of course. If I were an infertile patient, headlines like these would be enough to make me consider cancelling my appointment to the fertility clinic. These news items all refer to a study recently published in the New England Journal of Medicine entitled, " Reproductive Technologies and the Risk of Birth Defects". (Here is a link to the original research article: http://www.nejm.org/doi/pdf/10.1056/NEJMoa1008095.)

The good news? The study actually showed that most fertility treatments do not appear to increase the risk of birth defects. In fact, here is the last paragraph of the second story listed above (from the New York Times):  

"“We can now state that a cycle of a single fresh embryo transfer with I.V.F. and, if necessary, followed by the transfer of a frozen embryo will result in no significant additional risk above that of a spontaneous conception,” [the lead author of the study] said." (My emphasis added)

So why the inconsistency? There are several studies that show the prevalence of birth defects is higher among children conceived using fertility treatments than in the general population. If you look hard enough, you can even find a couple of papers that implicate clomiphene in birth defects (a scary thought given that this is the most commonly used fertility drug in the US; in 1991, more than 700,000 clomiphene prescriptions were filled, and I'm confident the number is higher now.) The problem with these studies is that it is not appropriate to compare infertile women with women in the general population. Women who conceive without infertility treatment are generally younger and have different socioeconomic, ethnic, and work backgrounds, and infertile women who conceive are more likely to have never had a baby before. One never knows whether it is the fertility treatment or the underlying differences among the infertile women that are responsible for the observed effects. Ideally, we should compare the birth defect rates among children of women who conceive using fertility treatment to those who conceive spontaneously. The problem with such a study is obvious - infertile women don't often conceive spontaneously, so it is hard to find suitable controls. (And even then, infertile women who conceive spontaneously are probably different from infertile women who conceive using fertility treatment - they tend to be younger, for one thing.)

But the investigators in the study cited above did just that, linking a South Australian registry of over 300,000 births to registries of assisted conception treatment, birth defects, and fertility clinic data.  They compared the rates of birth defects in the children of fertile women to those of infertile women who had conceived spontaneously or using a variety of infertility treatments. They also attempted to adjust the risks based on factors thought to be associated with adverse pregnancy outcomes. Here are the factors they accounted for: "parity, fetal sex, year of birth, maternal race or ethnic group, maternal country of birth, maternal conditions in pregnancy (preexisting hypertension, pregnancy-induced hypertension, preexisting diabetes, gestational diabetes, anemia, urinary tract infection, epilepsy, and asthma), maternal smoking during pregnancy, socioeconomic disadvantage on the basis of the postal code of the mother’s residence (according to the Socio-economic Indexes for Areas), and maternal and paternal occupation".
And here is the conclusion of the study: "The increased risk of birth defects associated with IVF was no longer significant after adjustment for parental factors. The risk of birth defects associated with ICSI remained increased after multivariate adjustment, although the possibility of residual confounding cannot be excluded."

In other words, the observed increase in birth defects seen after IVF (about 1.5 times the baseline) was due to patient characteristics rather than the IVF procedure itself. Good news for prospective IVF patients! But what about the increased risk with intracytoplasmic sperm injection (ICSI)? I think this is most likely due to patient confounding, too, as ICSI is frequently done for male factor infertility, and in couples where the husband (who is often much older than the wife) has had a vasectomy. Older men are slightly more likely to father children with certain birth defects (which is why the recommended age limit for men to donate sperm is 39).  Unfortunately, the investigators had no information about the age of the man in this study, so they couldn't control for that variable. (And shame on them for not getting this information.)

Also, the condition of male infertility may itself by linked with other conditions that might increase the risk of birth defects. One example of this is cystic fibrosis. Men carrying the gene for cystic fibrosis may have absence of the vas deferens, and these men typically require sperm aspiration with ICSI to father a pregnancy. (In fact, the relationship between congenital absence of the vas deferens and cystic fibrosis was first recognized only after cystic fibrosis was frequently noted among offspring conceived using IVF after sperm aspiration). 

There were a few other findings in this study worth noting:

- The birth defect rate among the general population was almost 6% - higher than most people (including most physicians) realize, but consistent with other studies. This is your baseline risk and is (mostly) independent of age. I tell patients to expect a 3% major and 3% minor birth defect risk in any birth, regardless of how the child was conceived.

- There was no particular syndrome that stood out among children conceived using IVF or ICSI (this is reassuring that the procedure itself is probably not inducing a birth defect).

- The birth defect rates were the same in children conceived using fresh and previously frozen embryos.

- "Medically supervised ovulation induction" was not associated with an increased birth defect rate, but "clomiphene citrate at home" was associated with a threefold increase in birth defects, even after controlling for other variables.  The authors had no explanation for this, and the number of births was small, so it may just be a spurious finding.  (I'm not sure what "clomiphene at home" means, anyway.)

So there is both good and bad news about birth defects and infertility. The good news is that fertility treatment (except maybe ICSI) does not increase the risk of birth defects.  The bad news is that infertile women are more likely to have underlying problems that do increase that risk, regardless of how their child is conceived.  I think the bottom line is: Get as healthy as possible before you get pregnant, and don't do ICSI unless your doctor thinks you really need it to achieve fertilization in your IVF cycle.  In fact, I think you shouldn't do any fertility treatment unless there is some reasonable data to support that doing it will improve your chances of conceiving.

And don't believe everything you read in the the news.



Tuesday, July 24, 2012

Does a hysterosalpingogram make you more fertile? Update

If you have read my earlier posts, you know I believe that using Ethiodol (oil-based contrast medium) for a hysterosalpingogram increases the post-procedure pregnancy rate. Unfortunately, the only US source for Ethiodol announced in March of 2010 that they were shutting down production "for marketing reasons". Since then, limited supplies of a similar product (Lipiodol Ultra-Fluide) have been made available in the US by FDA-approved importation from a French manufacturer; the current distributor is Guerbet USA. I called up Guerbet today to see if I could buy some Lipiodol Ultra-Fluide, but alas, it is only being made available for use in "life-saving medical procedures", and even if they would sell it to me, one 10 mL ampoule would cost $590 (ouch!).

The company rep said they hope to have Ethiodol back on the market within a year.


Monday, July 23, 2012

Insulin sensitizers and polycystic ovary syndrome

I've recently received some requests to address the role of insulin sensitizers for the treatment of polycystic ovary syndrome, in particular D-chiro-inositol. Here are my thoughts as of 7-23-2012.

Many women with PCOS have insulin resistance, and there are a variety of drugs which improve insulin sensitivity. These drugs include metformin, troglitazone, rosiglitazone, pioglitazone, D-chiro-inositol, and myo-inositol. Their actions on insulin release and action are rather complex, but it is useful to just consider them all as acting to improve the effect of insulin in the body.

Now, I think there is fairly good evidence that treatment with an insulin sensitizer improves ovarian function in women with PCOS. (Yes, I did participate in one of the largest trials of metformin for PCOS ever performed, which showed no benefit of metformin, but please hear me out.) Metformin is by far the most commonly used insulin sensitizer in PCOS patients. My take on the medical literature is that metformin is most beneficial in PCOS patients who are obese. (The study I participated in wasn't sufficiently powered to show this, but in that study the ovulation rate in PCOS patients with BMI over 34 who were on clomiphene was improved by adding metformin) . It does promote weight loss in these women, which probably ameliorates the syndrome a bit, but it also has some action independent of weight loss. In particular, metformin may improve the response to clomiphene in obese PCOS patients (and that is the patient for whom I most commonly prescribe metformin). However, clomiphene is much more likely to induce ovulation and pregnancy in PCOS patients than metformin. I often start obese PCOS patients on metformin for a couple of months and then add clomiphene if they are not ovulating on the metformin alone.

There is much less known about the effects of the other insulin sensitizers on PCOS, but they probably have some benefit, too. I don't use them, though. The published data on the inositol derivatives is limited and contradictory. There is even one paper that claims D-chiro-inositol worsens egg quality in infertile women. More worrisome is that some insulin sensitizers have been shown to have serious side effects, and this information didn't come to light until the drugs were widely prescribed. Troglitazone (Rezulin) is a good example. Years ago, it was held up as the "next generation metformin", with better efficacy and fewer side effects. It did work some on PCOS, but it was also found to cause liver failure and was pulled from the market. Pioglitazone (Actos) can cause heart failure.

For now, the only insulin sensitizer I use is metformin, and I don't use it all that often.


Wednesday, March 7, 2012

Thyroid problems

Thyroid disease has been linked to menstrual irregularity, infertility, and miscarriage (as well as many other medical problems). I think that anyone with difficulty conceiving, irregular menses, or a history of miscarriage or preterm delivery should have TSH, free T4, and thyroid peroxidase antibody levels checked. Be careful if your doctor or nurse says your TSH level is OK, because even levels in the high-normal range (greater than 2.5) probably need to be treated.

Iodine is necessary for normal thyroid function, and more than one third of reproductive-age women in the US don't get enough iodine. In my opinion, all women attempting pregnancy should take a prenatal vitamin that contains at least 150 mcg of iodine (and 220 mcg may be better). The iodine in the vitamin should be not be derived from kelp, as the levels of iodine in kelp vary dramatically. I recently made a trip to the CVS pharmacy, and I was disappointed to see that fewer than half of the prenatal vitamins contained iodine, and some of ones that did listed kelp as the iodine source. The only over-the-counter prenatal vitamin I found at CVS that had 220 mcg of iodine was Centrum Specialist Prenatal. (I have no financial ties to the company that makes this vitamin.) By the way, prescription prenatal vitamins are no more likely to have iodine than over-the-counter brands.