Four Changes That Are Here to Stay

We live in a rapidly changing world and keeping abreast of technology and evolving “best practices” can be challenging. Even with our instant digital access and social networking, assessing where we stand with regard to our adoption of newer trends can be daunting. With that caveat in the forefront, here are four topics in obstetrics and gynecology that we believe merit your attention.

New US Preventive Services Task Force Cervical Cancer Screening Guidelines

In March 2012, the US Preventive Services Task Force (USPSTF) introduced new guidelines for cervical cancer screening that significantly alter the traditional standard of the yearly Papanicolaou test that many physicians have relied upon for years. Although it is true that for some time neither the USPSTF nor the American Congress of Obstetricians and Gynecologists has endorsed annual Papanicolaou tests from age 18 to death, the newer guidelines are even further from this model and formally promote cotesting with cervical cytology (Papanicolaou tests) and human papillomavirus (HPV) testing. Care providers providing cervical cancer screening should familiarize themselves with these new recommendations and remember these are guidelines only for screening. The basics tenets are presented below; a more robust explanation can be found on the USPSFT Web site.¹

1. Women aged 21 to 65: Screen with cytology (Papanicolaou test) every 3 years.

2. Women aged 30 to 65: Screen with cytology every 3 years or cotesting (cytology/HPV testing) every 5 years.

3. Women < 21: Do not screen.

4. Women > 65 who have had adequate prior screening and are not high risk: Do not screen.

5. Women after hysterectomy with removal of the cervix with no history of high-grade precancer or cervical cancer: Do not screen.

6. Women < 30: Do not screen with HPV testing (alone or with cytology).

Minimally Invasive Gynecologic Surgery

Including minimally invasive gynecologic surgery (MIGS) in an editorial on new concepts presents a certain irony because gynecologists have been at the vanguard of minimally invasive surgery for at least the past century. To be sure, there are still excellent reasons to open patients and good clinical judgment should always prevail. However, in the United States in 2012, too many hysterectomies, myomectomies, and complex gynecologic procedures were still performed via laparotomy. Whether the approach is vaginal, traditional straight stick, robot-assisted, three-dimensional, or single port, there are sufficient MIGS options, skilled surgeons, and training opportunities for our collective discipline to finally say “enough.” Laparoscopic cholecystectomies have long since replaced open surgeries as the standard of care in general surgery and the time has come for gynecologists without MIGS training to learn the skills or stop doing the procedures.

Noninvasive Prenatal Testing Using Massively Parallel Genetic Sequencing

The term noninvasive prenatal testing (NIPT) refers to prenatal testing for fetal aneuploidy performed on a blood sample drawn from the mother. It is a screening test that can help women determine if their fetus is at high or low risk for trisomy (an extra copy of a chromosome) or monosomy (a missing chromosome) in a minimally invasive manner. In this way, it is analogous to first-trimester risk assessment (which includes the sonographic nuchal translucency measurement and two serum analyte markers in the maternal blood at approximately 11–14 weeks) and the maternal “quad screen” (a series of four biomarkers measured in the mother’s blood at 15–20 weeks). All of these screening tests should be distinguished from diagnostic tests (such as amniocentesis or chorionic villus sampling [CVS]), which can effectively definitively confirm or refute the diagnosis of fetal aneuploidy.

During pregnancy, fetal cells are constantly trafficking across the placenta into the maternal circulation. It has been estimated that, after the first trimester, there is approximately 1 fetal cell for every 10,000 maternal cells. Efforts to isolate these fetal cells for karyotype analysis have been largely unsuccessful. For this reason, attention has focused on the analysis of cell-free fetal DNA. Approximately 5% to 10% of the cell-free DNA in the maternal circulation comes from the pregnancy, most of which is shed from the placenta. Unfortunately, the absolute amount of fetal DNA is very small, typically < 1 μg/20 mL of blood, and separating the fetal DNA from maternal DNA is not technically possible at this time. The term massively parallel genetic sequencing (also called next-generation sequencing or second-generation sequencing) refers to several high-throughput approaches to DNA sequencing, all of which use miniaturized platforms for sequencing large numbers of small DNA sequences in a flow cell. Moreover, multiplex platforms have been developed that allow DNA samples from multiple patients to be sequenced in the same flow cells, thereby decreasing the cost. For NIPT, this approach allows for multiple small fragments of DNA (typically 36 bp in length) to be sequenced simultaneously using primers selective to particular chromosomes (eg, chromosomes 21, 18, 13, X, and Y). The amount of transcript measured can then be compared with what would be expected if the fetal karyotype were normal (euploid). A number of companies have been spearheading the effort to develop a reliable and commercially viable NIPT, including Sequenom Center for Molecular Medicine (San Diego, CA), Verinata Health (Redwood City, CA), Ariosa Diagnostics (San Jose, CA), and Natera (San Carlos, CA). Although the precise technology may vary, the message is the same: these are screening tests performed by analyzing cell-free fetal DNA in a sample of maternal blood collected as early as the first trimester. And all positive test results should be confirmed by amniocentesis or CVS.

Progesterone Therapy to Prevent Preterm Birth

On February 3, 2011, the US Food and Drug Administration (FDA) approved the use of progesterone supplementation—specifically, hydroxyprogesterone caproate injections (Makena™; Ther-Rx, Bridgeton, MO)—to reduce the risk of recurrent preterm birth in women with a singleton pregnancy who have a history of at least one prior spontaneous preterm delivery.² The recommended regimen is 250 mg intramuscularly every week from 16 to 20 weeks through 36 weeks of gestation. Although progesterone supplementation is not a panacea for the prevention of all preterm deliveries (indeed, it will prevent only one out of three cases of recurrent preterm births in high-risk women), it is the only intervention that has been shown to be effective in preventing preterm deliveries in the past 4 decades. Many questions remain: What is the correct formulation? What is the correct dose and route of administration? Who should receive it? Recent data suggest that progesterone supplementation may also prevent preterm birth in women with cervical shortening in the second trimester (although this is not currently an FDA-approved indication), but not in women with uncomplicated twins. Given these data, all women at risk of preterm delivery by virtue of a prior spontaneous preterm birth should be counseled early in pregnancy about the potential benefits of progesterone supplementation.