OBG Management

EXPERT COMMENTARY

Because of women’s personal preference and aversion, for various reasons, to LARC methods, the current estimated use rate of 17% for LARC methods would increase only to 24% to 29% even if major barriers, such as cost and availability, were removed.¹ To gain more insight into this issue, Hubacher and colleagues sought to determine if LARC methods would meet the contraceptive needs and be acceptable to a population of women who were not seeking these methods actively and who might have some reservation about using them.

Details of the study

The authors approached women actively seeking 1 of the 2 SARC methods but not a LARC method for contraception. They enrolled 524 women into a cohort study in which they received their desired SARC method. In addition, 392 women agreed to be enrolled in a randomized clinical trial comparing women beginning a LARC method for the first time with a group receiving 1 of the 2 SARC methods.

Importance of covered costs. Of note, the women in the randomized trial had the costs of the insertion or removal of the LARC method covered; those randomly assigned to the comparative SARC arm had the costs of their oral contraceptives (OCs) or depot medroxyprogesterone acetate (DMPA) covered for the first year of use. Underwriting the costs in the randomized study was likely important for study recruitment, since 47% of participants who were randomized to the LARC group cited cost as one of the reasons they did not try a LARC method previously.

Satisfaction with contraceptive method. In addition to the differences in continuation rates and pregnancy rates noted, it is interesting that, among women who tried a LARC method and who had some persistent negative feelings about the method, 65.9% would try the method again.

Satisfaction levels were estimated using 3 choices, with “happiness” being the highest level of satisfaction, followed by “neutral” and “unhappy.” At 24 months, the number of women indicating happiness was similar among the 3 study groups: 71.4% for the LARC randomized group, 75.0% for the randomized SARC group, and 77.6% for the preferred SARC cohort group.

Among women who discontinued their LARC method, occurrence of adverse effects was the reason given 74.2% of the time, while among SARC method users in both groups there was no dominant reason for discontinuation. Also, among women who discontinued their method, the percentage indicating happiness was 32.2% for the LARC randomized group compared with 69.9% and 68.2% for the randomized and preference cohort SARC groups, respectively.
 

Study strengths and weaknesses

This study had several strengths. The population from which the study groups were obtained was demographically diverse and was appropriate for determining if women with reservations about LARC methods could have satisfactory outcomes similar to women who self-select LARC methods. Further, the 24 months of observations indicate that, for the most part, satisfaction persisted.

One of the study’s shortcomings is the limited data on the subsets, that is, the specific method chosen, within each of the study groups.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

Because of women’s personal preference and aversion, for various reasons, to LARC methods, the current estimated use rate of 17% for LARC methods would increase only to 24% to 29% even if major barriers, such as cost and availability, were removed.¹ To gain more insight into this issue, Hubacher and colleagues sought to determine if LARC methods would meet the contraceptive needs and be acceptable to a population of women who were not seeking these methods actively and who might have some reservation about using them.

Details of the study

The authors approached women actively seeking 1 of the 2 SARC methods but not a LARC method for contraception. They enrolled 524 women into a cohort study in which they received their desired SARC method. In addition, 392 women agreed to be enrolled in a randomized clinical trial comparing women beginning a LARC method for the first time with a group receiving 1 of the 2 SARC methods.

Importance of covered costs. Of note, the women in the randomized trial had the costs of the insertion or removal of the LARC method covered; those randomly assigned to the comparative SARC arm had the costs of their oral contraceptives (OCs) or depot medroxyprogesterone acetate (DMPA) covered for the first year of use. Underwriting the costs in the randomized study was likely important for study recruitment, since 47% of participants who were randomized to the LARC group cited cost as one of the reasons they did not try a LARC method previously.

Satisfaction with contraceptive method. In addition to the differences in continuation rates and pregnancy rates noted, it is interesting that, among women who tried a LARC method and who had some persistent negative feelings about the method, 65.9% would try the method again.

Satisfaction levels were estimated using 3 choices, with “happiness” being the highest level of satisfaction, followed by “neutral” and “unhappy.” At 24 months, the number of women indicating happiness was similar among the 3 study groups: 71.4% for the LARC randomized group, 75.0% for the randomized SARC group, and 77.6% for the preferred SARC cohort group.

Among women who discontinued their LARC method, occurrence of adverse effects was the reason given 74.2% of the time, while among SARC method users in both groups there was no dominant reason for discontinuation. Also, among women who discontinued their method, the percentage indicating happiness was 32.2% for the LARC randomized group compared with 69.9% and 68.2% for the randomized and preference cohort SARC groups, respectively.
 

Study strengths and weaknesses

This study had several strengths. The population from which the study groups were obtained was demographically diverse and was appropriate for determining if women with reservations about LARC methods could have satisfactory outcomes similar to women who self-select LARC methods. Further, the 24 months of observations indicate that, for the most part, satisfaction persisted.

One of the study’s shortcomings is the limited data on the subsets, that is, the specific method chosen, within each of the study groups.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

Because of women’s personal preference and aversion, for various reasons, to LARC methods, the current estimated use rate of 17% for LARC methods would increase only to 24% to 29% even if major barriers, such as cost and availability, were removed.¹ To gain more insight into this issue, Hubacher and colleagues sought to determine if LARC methods would meet the contraceptive needs and be acceptable to a population of women who were not seeking these methods actively and who might have some reservation about using them.

Details of the study

The authors approached women actively seeking 1 of the 2 SARC methods but not a LARC method for contraception. They enrolled 524 women into a cohort study in which they received their desired SARC method. In addition, 392 women agreed to be enrolled in a randomized clinical trial comparing women beginning a LARC method for the first time with a group receiving 1 of the 2 SARC methods.

Importance of covered costs. Of note, the women in the randomized trial had the costs of the insertion or removal of the LARC method covered; those randomly assigned to the comparative SARC arm had the costs of their oral contraceptives (OCs) or depot medroxyprogesterone acetate (DMPA) covered for the first year of use. Underwriting the costs in the randomized study was likely important for study recruitment, since 47% of participants who were randomized to the LARC group cited cost as one of the reasons they did not try a LARC method previously.

Satisfaction with contraceptive method. In addition to the differences in continuation rates and pregnancy rates noted, it is interesting that, among women who tried a LARC method and who had some persistent negative feelings about the method, 65.9% would try the method again.

Satisfaction levels were estimated using 3 choices, with “happiness” being the highest level of satisfaction, followed by “neutral” and “unhappy.” At 24 months, the number of women indicating happiness was similar among the 3 study groups: 71.4% for the LARC randomized group, 75.0% for the randomized SARC group, and 77.6% for the preferred SARC cohort group.

Among women who discontinued their LARC method, occurrence of adverse effects was the reason given 74.2% of the time, while among SARC method users in both groups there was no dominant reason for discontinuation. Also, among women who discontinued their method, the percentage indicating happiness was 32.2% for the LARC randomized group compared with 69.9% and 68.2% for the randomized and preference cohort SARC groups, respectively.
 

Study strengths and weaknesses

This study had several strengths. The population from which the study groups were obtained was demographically diverse and was appropriate for determining if women with reservations about LARC methods could have satisfactory outcomes similar to women who self-select LARC methods. Further, the 24 months of observations indicate that, for the most part, satisfaction persisted.

One of the study’s shortcomings is the limited data on the subsets, that is, the specific method chosen, within each of the study groups.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Learn more about NAMS: http://www.menopause.org/home

Learn more about NAMS: http://www.menopause.org/home

Learn more about NAMS: http://www.menopause.org/home

Investigators from the National Institutes of Health and Shady Grove Fertility found that among women having a singleton live birth resulting from in vitro fertilization (IVF) that black women are at higher risk for lower gestational age and preterm delivery than white women.¹ The study results were presented at the American Society for Reproductive Medicine (ASRM) 2018 annual meeting (October 6 to 10, Denver, Colorado).

Kate Devine, MD, coinvestigator of the retrospective cohort study said in an interview with OBG Management that “It’s been well documented that African Americans have a higher preterm birth rate in the United States compared to Caucasians and the overall population. While the exact mechanism of preterm birth is unknown and likely varied, and while the mechanism for the preterm birth rate being higher in African Americans is not well understood, it has been hypothesized that socioeconomic factors are responsible at least in part.”² She added that the investigators used a population of women receiving IVF for the study because “access to reproductive care and IVF is in some way a leveling factor in terms of socioeconomics.”

Details of the study. The investigators reviewed all singleton IVF pregnancies ending in live birth among women self-identifying as white, black, Asian, or Hispanic from 2004 to 2016 at a private IVF practice (N=10,371). The primary outcome was gestational age at birth, calculated as the number of days from oocyte retrieval to birth, plus 14, among white, black, Asian, and Hispanic women receiving IVF.

Births among black women occurred more than 6 days earlier than births among white women. The researchers noted that some of the shorter gestations among the black women could be explained by the higher average body mass index of the group (P<.0001). Dr. Devine explained that another contributing factor was the higher incidence of fibroid uterus among the black women (P<.0001). But after adjusting for these and other demographic variables, the black women still delivered 5.5 days earlier than the white women, and they were more than 3 times as likely to have either very preterm or extremely preterm deliveries (TABLE).¹

Investigators from the National Institutes of Health and Shady Grove Fertility found that among women having a singleton live birth resulting from in vitro fertilization (IVF) that black women are at higher risk for lower gestational age and preterm delivery than white women.¹ The study results were presented at the American Society for Reproductive Medicine (ASRM) 2018 annual meeting (October 6 to 10, Denver, Colorado).

Kate Devine, MD, coinvestigator of the retrospective cohort study said in an interview with OBG Management that “It’s been well documented that African Americans have a higher preterm birth rate in the United States compared to Caucasians and the overall population. While the exact mechanism of preterm birth is unknown and likely varied, and while the mechanism for the preterm birth rate being higher in African Americans is not well understood, it has been hypothesized that socioeconomic factors are responsible at least in part.”² She added that the investigators used a population of women receiving IVF for the study because “access to reproductive care and IVF is in some way a leveling factor in terms of socioeconomics.”

Details of the study. The investigators reviewed all singleton IVF pregnancies ending in live birth among women self-identifying as white, black, Asian, or Hispanic from 2004 to 2016 at a private IVF practice (N=10,371). The primary outcome was gestational age at birth, calculated as the number of days from oocyte retrieval to birth, plus 14, among white, black, Asian, and Hispanic women receiving IVF.

Births among black women occurred more than 6 days earlier than births among white women. The researchers noted that some of the shorter gestations among the black women could be explained by the higher average body mass index of the group (P<.0001). Dr. Devine explained that another contributing factor was the higher incidence of fibroid uterus among the black women (P<.0001). But after adjusting for these and other demographic variables, the black women still delivered 5.5 days earlier than the white women, and they were more than 3 times as likely to have either very preterm or extremely preterm deliveries (TABLE).¹

Investigators from the National Institutes of Health and Shady Grove Fertility found that among women having a singleton live birth resulting from in vitro fertilization (IVF) that black women are at higher risk for lower gestational age and preterm delivery than white women.¹ The study results were presented at the American Society for Reproductive Medicine (ASRM) 2018 annual meeting (October 6 to 10, Denver, Colorado).

Kate Devine, MD, coinvestigator of the retrospective cohort study said in an interview with OBG Management that “It’s been well documented that African Americans have a higher preterm birth rate in the United States compared to Caucasians and the overall population. While the exact mechanism of preterm birth is unknown and likely varied, and while the mechanism for the preterm birth rate being higher in African Americans is not well understood, it has been hypothesized that socioeconomic factors are responsible at least in part.”² She added that the investigators used a population of women receiving IVF for the study because “access to reproductive care and IVF is in some way a leveling factor in terms of socioeconomics.”

Details of the study. The investigators reviewed all singleton IVF pregnancies ending in live birth among women self-identifying as white, black, Asian, or Hispanic from 2004 to 2016 at a private IVF practice (N=10,371). The primary outcome was gestational age at birth, calculated as the number of days from oocyte retrieval to birth, plus 14, among white, black, Asian, and Hispanic women receiving IVF.

Births among black women occurred more than 6 days earlier than births among white women. The researchers noted that some of the shorter gestations among the black women could be explained by the higher average body mass index of the group (P<.0001). Dr. Devine explained that another contributing factor was the higher incidence of fibroid uterus among the black women (P<.0001). But after adjusting for these and other demographic variables, the black women still delivered 5.5 days earlier than the white women, and they were more than 3 times as likely to have either very preterm or extremely preterm deliveries (TABLE).¹

Investigators from the Stanford Hospital and Clinics in California found that while absolute risk is low, women who have received an infertility diagnosis or who have received fertility treatment are at higher risk of several markers of severe maternal morbidity than women who never received an infertility diagnosis or fertility treatment.¹ The study results were presented at the American Society for Reproductive Medicine (ASRM) 2018 annual meeting (October 6 to 10, Denver, Colorado).

Gaya Murugappan, MD, lead investigator on the study, explained in an interview with OBG Management, “We know that in the last decade or so the rate of maternal morbidity has been rising gradually in the US, and we know that the utilization of fertility technology and the incidence of infertility are also rising.” The retrospective analysis set out to determine if a connection exists.

Methods. The investigators used a large insurance claims database to look at data from 2003 to 2016. They identified a group of infertile women who later conceived without fertility treatment (n=1822 deliveries) and a group of women who received fertility treatment (n=782 deliveries) and compared them with a control group of women who never received an infertility diagnosis or fertility treatment (n=37,944 deliveries). Women who currently or previously had cancer were excluded from the study.

The primary outcome was the number of indicators of severe maternal morbidity that occurred during the 6 months prior to or following delivery.

Findings. Compared with the control group, the women diagnosed with infertility were almost 4 times as likely to experience severe anesthesia complications (0.38% vs 0.11%; odds ratio [OR], 3.83; 95% confidence interval [CI], 1.69–8.70), about twice as likely to experience intraoperative heart failure (0.71% vs 0.31%; OR, 1.88; 95% CI, 1.05–3.34), and more than 3 times as likely to receive a hysterectomy (1.04% vs 0.28%; OR, 3.30; 95% CI, 2.02–5.40).

Similarly, compared with controls, women who had received fertility treatment had an OR of 2.66 for disseminated intravascular coagulation (2.81% vs 0.91%; 95% CI, 1.66–4.24), an OR of 5.17 for shock (0.90% vs 0.15%; 95% CI, 2.21–12.06), an OR of 1.61 for blood transfusions (3.71% vs 1.64%; 95% CI, 1.07–2.42), and an OR of 1.43 for cardiac monitoring (13.17% vs 8.14%; 95% CI, 1.14–1.79).

More research is needed. Dr. Murugappan noted, “I hope that these data help us identify high-risk populations of women so that we can minimize the occurrence of these potentially devastating health outcomes. Women need to be telling their ObGyns that they have a history of infertility and/or fertility treatment. Some women may not want to say that they conceived with donor egg, for example, but that could be a critical element of a patient’s history that an ObGyn should be aware of.”

More study is necessary, she added. For instance, “a study in the future looking at risk of maternal morbidity in patients who are infertile but then who go on to conceive spontaneously. Then we can tease out what is the effect of infertility versus the effect of fertility treatment.”

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Investigators from the Stanford Hospital and Clinics in California found that while absolute risk is low, women who have received an infertility diagnosis or who have received fertility treatment are at higher risk of several markers of severe maternal morbidity than women who never received an infertility diagnosis or fertility treatment.¹ The study results were presented at the American Society for Reproductive Medicine (ASRM) 2018 annual meeting (October 6 to 10, Denver, Colorado).

Gaya Murugappan, MD, lead investigator on the study, explained in an interview with OBG Management, “We know that in the last decade or so the rate of maternal morbidity has been rising gradually in the US, and we know that the utilization of fertility technology and the incidence of infertility are also rising.” The retrospective analysis set out to determine if a connection exists.

Methods. The investigators used a large insurance claims database to look at data from 2003 to 2016. They identified a group of infertile women who later conceived without fertility treatment (n=1822 deliveries) and a group of women who received fertility treatment (n=782 deliveries) and compared them with a control group of women who never received an infertility diagnosis or fertility treatment (n=37,944 deliveries). Women who currently or previously had cancer were excluded from the study.

The primary outcome was the number of indicators of severe maternal morbidity that occurred during the 6 months prior to or following delivery.

Findings. Compared with the control group, the women diagnosed with infertility were almost 4 times as likely to experience severe anesthesia complications (0.38% vs 0.11%; odds ratio [OR], 3.83; 95% confidence interval [CI], 1.69–8.70), about twice as likely to experience intraoperative heart failure (0.71% vs 0.31%; OR, 1.88; 95% CI, 1.05–3.34), and more than 3 times as likely to receive a hysterectomy (1.04% vs 0.28%; OR, 3.30; 95% CI, 2.02–5.40).

Similarly, compared with controls, women who had received fertility treatment had an OR of 2.66 for disseminated intravascular coagulation (2.81% vs 0.91%; 95% CI, 1.66–4.24), an OR of 5.17 for shock (0.90% vs 0.15%; 95% CI, 2.21–12.06), an OR of 1.61 for blood transfusions (3.71% vs 1.64%; 95% CI, 1.07–2.42), and an OR of 1.43 for cardiac monitoring (13.17% vs 8.14%; 95% CI, 1.14–1.79).

More research is needed. Dr. Murugappan noted, “I hope that these data help us identify high-risk populations of women so that we can minimize the occurrence of these potentially devastating health outcomes. Women need to be telling their ObGyns that they have a history of infertility and/or fertility treatment. Some women may not want to say that they conceived with donor egg, for example, but that could be a critical element of a patient’s history that an ObGyn should be aware of.”

More study is necessary, she added. For instance, “a study in the future looking at risk of maternal morbidity in patients who are infertile but then who go on to conceive spontaneously. Then we can tease out what is the effect of infertility versus the effect of fertility treatment.”

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Investigators from the Stanford Hospital and Clinics in California found that while absolute risk is low, women who have received an infertility diagnosis or who have received fertility treatment are at higher risk of several markers of severe maternal morbidity than women who never received an infertility diagnosis or fertility treatment.¹ The study results were presented at the American Society for Reproductive Medicine (ASRM) 2018 annual meeting (October 6 to 10, Denver, Colorado).

Gaya Murugappan, MD, lead investigator on the study, explained in an interview with OBG Management, “We know that in the last decade or so the rate of maternal morbidity has been rising gradually in the US, and we know that the utilization of fertility technology and the incidence of infertility are also rising.” The retrospective analysis set out to determine if a connection exists.

Methods. The investigators used a large insurance claims database to look at data from 2003 to 2016. They identified a group of infertile women who later conceived without fertility treatment (n=1822 deliveries) and a group of women who received fertility treatment (n=782 deliveries) and compared them with a control group of women who never received an infertility diagnosis or fertility treatment (n=37,944 deliveries). Women who currently or previously had cancer were excluded from the study.

The primary outcome was the number of indicators of severe maternal morbidity that occurred during the 6 months prior to or following delivery.

Findings. Compared with the control group, the women diagnosed with infertility were almost 4 times as likely to experience severe anesthesia complications (0.38% vs 0.11%; odds ratio [OR], 3.83; 95% confidence interval [CI], 1.69–8.70), about twice as likely to experience intraoperative heart failure (0.71% vs 0.31%; OR, 1.88; 95% CI, 1.05–3.34), and more than 3 times as likely to receive a hysterectomy (1.04% vs 0.28%; OR, 3.30; 95% CI, 2.02–5.40).

Similarly, compared with controls, women who had received fertility treatment had an OR of 2.66 for disseminated intravascular coagulation (2.81% vs 0.91%; 95% CI, 1.66–4.24), an OR of 5.17 for shock (0.90% vs 0.15%; 95% CI, 2.21–12.06), an OR of 1.61 for blood transfusions (3.71% vs 1.64%; 95% CI, 1.07–2.42), and an OR of 1.43 for cardiac monitoring (13.17% vs 8.14%; 95% CI, 1.14–1.79).

More research is needed. Dr. Murugappan noted, “I hope that these data help us identify high-risk populations of women so that we can minimize the occurrence of these potentially devastating health outcomes. Women need to be telling their ObGyns that they have a history of infertility and/or fertility treatment. Some women may not want to say that they conceived with donor egg, for example, but that could be a critical element of a patient’s history that an ObGyn should be aware of.”

More study is necessary, she added. For instance, “a study in the future looking at risk of maternal morbidity in patients who are infertile but then who go on to conceive spontaneously. Then we can tease out what is the effect of infertility versus the effect of fertility treatment.”

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Investigators from the University of Texas Southwestern are dispelling the myth that you shouldn’t recommend intrauterine devices (IUDs) for nulliparous women because the devices might make it more difficult for them to become pregnant after discontinuation. They found that nulliparous women can just as easily get pregnant after using a progestin intrauterine system (IUS) as parous women,¹ according to results of a study presented at the American Society for Reproductive Medicine (ASRM) 2018 annual meeting (October 6–10, Denver, Colorado).

Bruce R. Carr, MD, lead investigator of the study, explained in an interview with OBG Management, “There have been a number of studies—maybe 10 to 15 years ago—that looked at pregnancy rates when patients stopped using IUDs, but most of these studies were done in women who were multiparous. There is almost no data on patients who are nulliparous stopping an IUD and trying to get pregnant.”

Participants and methods. This prospective, multicenter, clinical trial, which is still ongoing, is evaluating the efficacy and safety for up to 10 years of the Liletta levonorgestrel 52-mg IUS in nulliparous and parous women ages 16 to 45 years. Every 3 months for up to 1 year, the investigators contacted the women who discontinued the IUS during the first 5 years of use and who were trying to become pregnant to determine pregnancy status.

Outcomes. The primary outcome was time to pregnancy among nulliparous vs parous women after discontinuation of a progestin IUS.

Findings. Overall, 132 (87%) of 152 women ages 16 to 35 years at the beginning of the study who attempted to become pregnant did so within 1 year of discontinuing the IUS, and there was no difference in pregnancy rates between nulliparous and parous women (87.5% vs 86.1%, respectively; P<.82) or between nulligravid and gravid women (88.2% vs 85.7%, respectively; P<.81). High percentages of women became pregnant by the end of 3 months (43.4%) and 6 months (69.7%), with a median time to conception of 91.5 days. The women used the IUS for a median of 34 months before discontinuation. Length of IUS use and age of the women at IUS discontinuation did not affect pregnancy rates at 12 months postdiscontinuation in either nulliparous or parous women (TABLE).¹

“The bottom line,” according to Dr. Carr, is that the “pregnancy rates were the same in women who had never been pregnant compared with women who had previously been pregnant.” He continued, “People worried that if a patient who had never been pregnant used an IUD that maybe she was going to have a harder time getting pregnant after discontinuing, and now we know that is not true. It [the study] reinforces the option of using progestin IUDs and not having to worry about future pregnancy.”

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

This article was updated October 15, 2018.

Investigators from the University of Texas Southwestern are dispelling the myth that you shouldn’t recommend intrauterine devices (IUDs) for nulliparous women because the devices might make it more difficult for them to become pregnant after discontinuation. They found that nulliparous women can just as easily get pregnant after using a progestin intrauterine system (IUS) as parous women,¹ according to results of a study presented at the American Society for Reproductive Medicine (ASRM) 2018 annual meeting (October 6–10, Denver, Colorado).

Bruce R. Carr, MD, lead investigator of the study, explained in an interview with OBG Management, “There have been a number of studies—maybe 10 to 15 years ago—that looked at pregnancy rates when patients stopped using IUDs, but most of these studies were done in women who were multiparous. There is almost no data on patients who are nulliparous stopping an IUD and trying to get pregnant.”

Participants and methods. This prospective, multicenter, clinical trial, which is still ongoing, is evaluating the efficacy and safety for up to 10 years of the Liletta levonorgestrel 52-mg IUS in nulliparous and parous women ages 16 to 45 years. Every 3 months for up to 1 year, the investigators contacted the women who discontinued the IUS during the first 5 years of use and who were trying to become pregnant to determine pregnancy status.

Outcomes. The primary outcome was time to pregnancy among nulliparous vs parous women after discontinuation of a progestin IUS.

Findings. Overall, 132 (87%) of 152 women ages 16 to 35 years at the beginning of the study who attempted to become pregnant did so within 1 year of discontinuing the IUS, and there was no difference in pregnancy rates between nulliparous and parous women (87.5% vs 86.1%, respectively; P<.82) or between nulligravid and gravid women (88.2% vs 85.7%, respectively; P<.81). High percentages of women became pregnant by the end of 3 months (43.4%) and 6 months (69.7%), with a median time to conception of 91.5 days. The women used the IUS for a median of 34 months before discontinuation. Length of IUS use and age of the women at IUS discontinuation did not affect pregnancy rates at 12 months postdiscontinuation in either nulliparous or parous women (TABLE).¹

“The bottom line,” according to Dr. Carr, is that the “pregnancy rates were the same in women who had never been pregnant compared with women who had previously been pregnant.” He continued, “People worried that if a patient who had never been pregnant used an IUD that maybe she was going to have a harder time getting pregnant after discontinuing, and now we know that is not true. It [the study] reinforces the option of using progestin IUDs and not having to worry about future pregnancy.”

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

This article was updated October 15, 2018.

Investigators from the University of Texas Southwestern are dispelling the myth that you shouldn’t recommend intrauterine devices (IUDs) for nulliparous women because the devices might make it more difficult for them to become pregnant after discontinuation. They found that nulliparous women can just as easily get pregnant after using a progestin intrauterine system (IUS) as parous women,¹ according to results of a study presented at the American Society for Reproductive Medicine (ASRM) 2018 annual meeting (October 6–10, Denver, Colorado).

Bruce R. Carr, MD, lead investigator of the study, explained in an interview with OBG Management, “There have been a number of studies—maybe 10 to 15 years ago—that looked at pregnancy rates when patients stopped using IUDs, but most of these studies were done in women who were multiparous. There is almost no data on patients who are nulliparous stopping an IUD and trying to get pregnant.”

Participants and methods. This prospective, multicenter, clinical trial, which is still ongoing, is evaluating the efficacy and safety for up to 10 years of the Liletta levonorgestrel 52-mg IUS in nulliparous and parous women ages 16 to 45 years. Every 3 months for up to 1 year, the investigators contacted the women who discontinued the IUS during the first 5 years of use and who were trying to become pregnant to determine pregnancy status.

Outcomes. The primary outcome was time to pregnancy among nulliparous vs parous women after discontinuation of a progestin IUS.

Findings. Overall, 132 (87%) of 152 women ages 16 to 35 years at the beginning of the study who attempted to become pregnant did so within 1 year of discontinuing the IUS, and there was no difference in pregnancy rates between nulliparous and parous women (87.5% vs 86.1%, respectively; P<.82) or between nulligravid and gravid women (88.2% vs 85.7%, respectively; P<.81). High percentages of women became pregnant by the end of 3 months (43.4%) and 6 months (69.7%), with a median time to conception of 91.5 days. The women used the IUS for a median of 34 months before discontinuation. Length of IUS use and age of the women at IUS discontinuation did not affect pregnancy rates at 12 months postdiscontinuation in either nulliparous or parous women (TABLE).¹

“The bottom line,” according to Dr. Carr, is that the “pregnancy rates were the same in women who had never been pregnant compared with women who had previously been pregnant.” He continued, “People worried that if a patient who had never been pregnant used an IUD that maybe she was going to have a harder time getting pregnant after discontinuing, and now we know that is not true. It [the study] reinforces the option of using progestin IUDs and not having to worry about future pregnancy.”

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

This article was updated October 15, 2018.

Citation: Raffaelli B, Neeb L, Israel-Willner, et al. Brain imaging in pregnant women with acute headache. J Neurol. 2018;265(8):1836–1843.

Citation: Raffaelli B, Neeb L, Israel-Willner, et al. Brain imaging in pregnant women with acute headache. J Neurol. 2018;265(8):1836–1843.

Citation: Raffaelli B, Neeb L, Israel-Willner, et al. Brain imaging in pregnant women with acute headache. J Neurol. 2018;265(8):1836–1843.

Recommended Resources:

• WomanLab.org
• Scientific Network on Female Sexual Health and Cancer

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Recommended Resources:

• WomanLab.org
• Scientific Network on Female Sexual Health and Cancer

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Recommended Resources:

• WomanLab.org
• Scientific Network on Female Sexual Health and Cancer

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Placenta accreta spectrum (PAS) describes abnormal invasion of placental tissue into or through the myometrium, comprising 3 distinct conditions: placenta accreta, placenta increta, and placenta percreta. This complication is relatively new to obstetrics, first described in 1937.¹

The overall incidence of PAS has been increasing over several decades, in parallel to an increasing rate of cesarean delivery (CD), with an incidence from 1982 through 2002 of 1 in 533 pregnancies, representing a 5-fold increase since the 1980s.² PAS is associated with significant morbidity and mortality, including fetal growth restriction, preterm delivery, placental abruption antenatally, and hemorrhage during delivery or postpartum.

Prenatal diagnosis of PAS and planned delivery at an experienced center are associated with significant reduction in maternal and fetal morbidity.³ In an era of advanced imaging modalities, prenatal detection of PAS regrettably remains variable and largely subjective: As many as 20% to 50% of cases of PAS escape prenatal diagnosis.^3,4

In this article, we review the sonographic markers of PAS, including diagnostic accuracy, and propose a standardized approach to prenatal diagnosis. Throughout our discussion, we describe protocols for detection of PAS practiced at our Maternal-Fetal Medicine Program in the Department of Obstetrics and Gynecology, Eastern Virginia Medical School (also see “US evaluation of PAS risk: The authors’ recommended approach”).

Numerous risk factors

There are many risk factors for PAS, including prior uterine surgery or instrumentation, such as CD, uterine curettage, myomectomy, pelvic radiation, and endometrial ablation. Other risk factors include smoking, in vitro fertilization, advanced maternal age, multiparity, and a brief interval between prior CD and subsequent pregnancy.⁵ Of major significance is the increased risk of PAS in the presence of placenta previa with prior CD.⁶ Knowledge of clinical risk factors by the interpreting physician appears to be associated with improved detection of PAS on ultrasonography (US).⁴

Ultrasonographic markers of PAS

First-trimester markers

Sonographic markers of PAS in the first trimester include:

• a gestational sac implanted in the lower uterine segment or in a CD scar
• multiple hypoechoic spaces within the placenta (lacunae).⁷

Lower uterine-segment implantation has been defined by Ballas and colleagues as 1) a gestational sac implanted in the lower one-third of the uterus between 8 and 10 weeks’ gestation or 2) a gestational sac occupying primarily the lower uterine segment from 10 weeks’ gestation onward (FIGURE 1).⁸ Our experience is that it is difficult to accurately assess lower uterine-segment implantation beyond 13 weeks of gestation because the sac typically expands to fill the upper uterine cavity.

Continue to: Color Doppler US...

Color Doppler US can help differentiate lower uterine-segment implantation from a gestational sac of a failed pregnancy in the process of expulsion by demonstrating loss of circumferential blood flow in the failed pregnancy. Furthermore, applying pressure to the anterior surface of the uterus will result in downward movement of the gestational sac of a failed pregnancy.⁹

Not all gestational sacs that implant in the lower uterine segment lead to PAS: Subsequent normal pregnancies have been reported in this circumstance. In such cases, a normal thick myometrium is noted anterior to the gestational sac.⁷ A patient with lower uterine-segment implantation without evidence of anterior myometrial thinning remains at risk for third-trimester placenta previa.⁷

Cesarean scar pregnancy carries significant risk of PAS. In these cases, the gestational sac is typically implanted within the scar, resulting in a thin anterior myometrium and significantly increased vascularity of the placental–myometrial and bladder–uterine wall interfaces (FIGURE 2).⁹ Differentiating cesarean scar pregnancy from a lower uterine-segment implantation is easier to perform before the eighth week of gestation but becomes more difficult as pregnancy advances. Although it might be useful to distinguish between true cesarean scar pregnancy and lower uterine-segment implantation adjacent to or involving the scar, both carry considerable risk of PAS and excessive hemorrhage, and the approach to treating both conditions is quite similar.

Lacunae, with or without documented blood flow on color Doppler US, are the third marker of PAS in the first trimester.⁸ Although some retrospective series and case reports describe the finding of lacunae in the first trimester of patients with diagnosed PAS, more recent literature suggests that these spaces are seen infrequently and at a similar frequency in women with and without PAS at delivery.⁷

Second- and third-trimester markers

Multiple diagnostic sonographic markers of PAS have been described in the second and third trimesters.

Placental location is a significant risk factor for PAS. Placenta previa in the setting of prior CD carries the highest risk of PAS—as high as 61% in women with both placenta previa and a history of 3 CDs.¹⁰ An anterior placenta appears to be a stronger risk factor for PAS than a posterior placenta in women with prior CD; the location of the placenta should therefore be evaluated in all women in the second trimester.

Continue to: Lacunae

Lacunae. The finding of multiple hypoechoic vascular spaces within the placental parenchyma has been associated with PAS (FIGURES 3 and 4). The pathogenesis of this finding is probably related to alterations in placental tissue resulting from long-term exposure to pulsatile blood flow.¹¹

Finberg and colleagues introduced a grading system for placental lacunae in 1992 that is still used:

• Grade 0: no lacunae seen
• Grade 1: 1 to 3 lacunae seen
• Grade 2: 4 to 6 lacunae seen
• Grade 3: multiple lacunae seen throughout the placenta.¹²

The sensitivity and specificity of lacunae as an independent marker for PAS have been reported to be 77% and 95%, respectively.¹³ Despite these findings, several studies report a range of sensitivity (73% to 100%) and negative predictive value (88% to 100%).¹⁴ Even in Finberg’s original work, 27% of cases of confirmed PAS had Grade 0 or Grade 1 placental lacunae and 11% of cases of placenta previa, without PAS, demonstrated Grade 2 lacunae.¹² There is agreement, however, that, the more lacunae, the higher the risk of PAS.

Continue to: Other US markers for PAS

Retroplacental–myometrial interface

Loss of the normal hypoechoic (clear) retroplacental zone, also referred to as loss of the clear space between placenta and uterus, is another marker of PAS (FIGURE 5). This finding corresponds to pathologic loss of the decidua basalis as trophoblastic tissue invades directly through the myometrium.¹⁵ This sonographic finding has been reported to have a detection rate of approximately 93%, with sensitivity of 52% and specificity of 57%, for PAS; the false-positive rate, however, has been in the range of 21% or higher. This marker should not be used alone because it is angle-dependent and can be found (as an absent clear zone) in normal anterior placentas.¹⁶

The strength of this US marker is in its negative predictive value, which ranges from 96% to 100%. The presence of a hypoechoic retroplacental clear space that extends the length of the placenta makes PAS unlikely.¹⁷ Of note, the clear zone may appear falsely absent as a result of increased pressure from the US probe.

Retroplacental myometrial thickness

Retroplacental myometrial thickness is difficult to assess because the lower uterine-segment myometrium thins in normal pregnancy as term approaches. This measurement also can be influenced by direct pressure of the US probe and fullness of the maternal bladder.¹⁸ In patients who have had a CD but who do not have PAS, the median myometrial thickness of the lower uterine segment in the third trimester is 2.4 mm.¹⁹

Thinning of the myometrium in the upper uterine segment always should be of concern. Studies of this marker have reported sensitivity of US ranging from 22% to 100% and specificity from 72% to 100%.^9,20 Given such variability, it is important to standardize the gestational age and sonographic approach for this marker.

Continue to: Uterovesical interface

Studies also have reported that abnormalities of the uterovesical interface are predictive of PAS. The uterovesical interface is best evaluated in a sagittal plane containing the lower uterine segment and a partially full bladder in gray-scale and color Doppler US.¹⁵ The normal uterovesical interface appears as a smooth line, without irregularities or increased vascularity on sagittal imaging.

Abnormalities include focal interruption of the hyperechoic bladder wall, bulging of the bladder wall, and increased vascularity, such as varicosities (FIGURES 5, 6, and 7).¹⁵ These findings may be seen as early as the first trimester but are more commonly noted in the second and third trimesters.⁷ The authors of a recent meta-analysis concluded that irregularity of the uterovesical interface is the most specific marker for invasive placentation (99.75% confidence interval; range, 99.5% to 99.9%).¹³

Other US markers and modalities

Three-dimensional US. Studies have evaluated the role of 3-dimensional (3D) US for predicting PAS. Application of 3D US in vascular mode has shown promise because it allows for semiquantitative assessment of placental vasculature.²² Using 3D US to screen for PAS presents drawbacks, however: The technology is not well-standardized and requires significant operator expertise for volume acquisition and manipulation. Prospective studies are needed before 3D US can be applied routinely to screen for and diagnose PAS.

Color Doppler US. As an adjunct to gray-scale US, color Doppler US can be used for making a diagnosis of PAS. Color Doppler US helps differentiate a normal subplacental venous complex with nonpulsatile, low-velocity venous blood flow waveforms from markedly dilated peripheral subplacental vascular channels with pulsatile venous-type flow, which suggests PAS. These vascular channels are often located directly over the cervix. In addition, the observation of bridging vessels linking the placenta and bladder with high diastolic arterial blood flow also suggests invasion.²¹ In a meta-analysis, overall sensitivity of color Doppler US for the diagnosis of PAS was 91%, with specificity of 87%.¹³

The value of utilizing multiple markers

The accuracy of US diagnosis of PAS is likely improved by using more than 1 sonographic marker. Pilloni and colleagues,²⁰ in a prospective analysis, found that 81% of cases of confirmed PAS had ≥2 markers and 51% of cases had ≥3 markers.

Several scoring systems have been proposed for making the diagnosis of PAS using combinations of sonographic markers, placental location, and clinical history.^19,24,25 In 2016, Tovbin and colleagues,²⁵ in a prospective study, evaluated a scoring system that included:

• number of previous CDs
• number of, maximum dimension of, and presence of blood flow in lacunae
• loss of uteroplacental clear zone
• placental location
• hypervascularity of the uterovesical or uteroplacental interface.

Tovbin assigned 1 or 2 points to each criterion. Each sonographic marker was found to be significantly associated with PAS when compared to a high-risk control group. A score of ≥8 was considered “at high risk” and predicted 69% of PAS cases.

Regrettably, no combination of US markers reliably predicts the depth of invasion of the placenta.²⁶

Continue to: A standardized approach is needed

To decrease variability and improve the US diagnosis of PAS, it is important to define and standardize the diagnosis of each sonographic marker for PAS.⁴ In 2016, the European Working Group on Abnormally Invasive Placenta (EW-AIP) proposed a set of US markers that always should be reported when performing an US examination for suspected abnormal placentation (TABLE).²³ Despite this effort by the EW-AIP, ambiguity remains over sonographic definitions of several PAS markers. For example, what determines a placental lacuna on US? And what constitutes an abnormal uterovesical interface? There is a need for a more objective definition of US markers of PAS and a standardized approach to the US examination in at-risk pregnancies.

The Society for Maternal-Fetal Medicine is coordinating a multi-society task force to address the need to define and standardize the US diagnosis of PAS.

Observations on other PAS diagnostic modalities

Magnetic resonance imaging

Adjunctive role. Magnetic resonance imaging (MRI) is often used as an adjunctive diagnostic modality in cases of suspected PAS. Several markers for PAS have been described on MRI, including¹⁵:

• intraplacental T2-weighted dark bands
• abnormal intraplacental vascularity
• heterogeneous intraplacental signal intensity
• focal interruption of the myometrium by the placenta
• uterine bulging.

Based on a recent meta-analysis, overall sensitivity of MRI for detecting PAS is 86% to 95%, with specificity of 80% to 95%. Although this is comparable to the sensitivity and specificity of US,²⁷ studies of MRI in PAS are smaller and more prone to bias than in studies of US, because MRI typically is used only in patients at highest risk for PAS. Few studies comparing US to MRI for PAS have been performed; all are small and lack statistical power.

Complementary role. MRI can be complementary to US in cases in which the placenta is posterior or located laterally²⁸ but, importantly, rarely changes decisions about surgical management when used in conjunction with US to assess patients for the diagnosis of PAS. (An exception might lie in the ability of MRI to assess the degree or depth of invasion of the placenta and discerning placenta percreta from placenta accreta.¹⁵)

Enhancement with contrast. Addition of gadolinium-based contrast might improve the ability of MRI to make a diagnosis of PAS, but gadolinium crosses the placenta barrier. Although fetal effects of gadolinium have not been observed, American College of Radiology guidelines recommend avoiding this contrast agent during pregnancy unless absolutely essential.²⁹

Specific indications. MRI without contrast should be considered 1) when US is inconclusive and 2) to further evaluate a posterior placenta suspicious for invasion, to define the precise topography of extrauterine placental invasion. The additional information offered by MRI might alter surgical planning.¹⁵

Biomarkers

Multiple serum biomarkers have been proposed to predict PAS in high-risk women. PAS might be associated with increased levels of first-trimester pregnancy-associated plasma protein A, second-trimester maternal serum alpha fetoprotein, and human chorionic gonadotropin, but studies of the utility of these biomarkers have yielded contradictory results.^30,31 Biomarkers are of interest and have significant clinical applicability, but none of the ones identified to date have high sensitivity or specificity for predicting PAS prenatally. Research is ongoing to identify markers of PAS that have sufficient predictive power.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Placenta accreta spectrum (PAS) describes abnormal invasion of placental tissue into or through the myometrium, comprising 3 distinct conditions: placenta accreta, placenta increta, and placenta percreta. This complication is relatively new to obstetrics, first described in 1937.¹

The overall incidence of PAS has been increasing over several decades, in parallel to an increasing rate of cesarean delivery (CD), with an incidence from 1982 through 2002 of 1 in 533 pregnancies, representing a 5-fold increase since the 1980s.² PAS is associated with significant morbidity and mortality, including fetal growth restriction, preterm delivery, placental abruption antenatally, and hemorrhage during delivery or postpartum.

Prenatal diagnosis of PAS and planned delivery at an experienced center are associated with significant reduction in maternal and fetal morbidity.³ In an era of advanced imaging modalities, prenatal detection of PAS regrettably remains variable and largely subjective: As many as 20% to 50% of cases of PAS escape prenatal diagnosis.^3,4

In this article, we review the sonographic markers of PAS, including diagnostic accuracy, and propose a standardized approach to prenatal diagnosis. Throughout our discussion, we describe protocols for detection of PAS practiced at our Maternal-Fetal Medicine Program in the Department of Obstetrics and Gynecology, Eastern Virginia Medical School (also see “US evaluation of PAS risk: The authors’ recommended approach”).

Numerous risk factors

There are many risk factors for PAS, including prior uterine surgery or instrumentation, such as CD, uterine curettage, myomectomy, pelvic radiation, and endometrial ablation. Other risk factors include smoking, in vitro fertilization, advanced maternal age, multiparity, and a brief interval between prior CD and subsequent pregnancy.⁵ Of major significance is the increased risk of PAS in the presence of placenta previa with prior CD.⁶ Knowledge of clinical risk factors by the interpreting physician appears to be associated with improved detection of PAS on ultrasonography (US).⁴

Ultrasonographic markers of PAS

First-trimester markers

Sonographic markers of PAS in the first trimester include:

• a gestational sac implanted in the lower uterine segment or in a CD scar
• multiple hypoechoic spaces within the placenta (lacunae).⁷

Lower uterine-segment implantation has been defined by Ballas and colleagues as 1) a gestational sac implanted in the lower one-third of the uterus between 8 and 10 weeks’ gestation or 2) a gestational sac occupying primarily the lower uterine segment from 10 weeks’ gestation onward (FIGURE 1).⁸ Our experience is that it is difficult to accurately assess lower uterine-segment implantation beyond 13 weeks of gestation because the sac typically expands to fill the upper uterine cavity.

Continue to: Color Doppler US...

Color Doppler US can help differentiate lower uterine-segment implantation from a gestational sac of a failed pregnancy in the process of expulsion by demonstrating loss of circumferential blood flow in the failed pregnancy. Furthermore, applying pressure to the anterior surface of the uterus will result in downward movement of the gestational sac of a failed pregnancy.⁹

Not all gestational sacs that implant in the lower uterine segment lead to PAS: Subsequent normal pregnancies have been reported in this circumstance. In such cases, a normal thick myometrium is noted anterior to the gestational sac.⁷ A patient with lower uterine-segment implantation without evidence of anterior myometrial thinning remains at risk for third-trimester placenta previa.⁷

Cesarean scar pregnancy carries significant risk of PAS. In these cases, the gestational sac is typically implanted within the scar, resulting in a thin anterior myometrium and significantly increased vascularity of the placental–myometrial and bladder–uterine wall interfaces (FIGURE 2).⁹ Differentiating cesarean scar pregnancy from a lower uterine-segment implantation is easier to perform before the eighth week of gestation but becomes more difficult as pregnancy advances. Although it might be useful to distinguish between true cesarean scar pregnancy and lower uterine-segment implantation adjacent to or involving the scar, both carry considerable risk of PAS and excessive hemorrhage, and the approach to treating both conditions is quite similar.

Lacunae, with or without documented blood flow on color Doppler US, are the third marker of PAS in the first trimester.⁸ Although some retrospective series and case reports describe the finding of lacunae in the first trimester of patients with diagnosed PAS, more recent literature suggests that these spaces are seen infrequently and at a similar frequency in women with and without PAS at delivery.⁷

Second- and third-trimester markers

Multiple diagnostic sonographic markers of PAS have been described in the second and third trimesters.

Placental location is a significant risk factor for PAS. Placenta previa in the setting of prior CD carries the highest risk of PAS—as high as 61% in women with both placenta previa and a history of 3 CDs.¹⁰ An anterior placenta appears to be a stronger risk factor for PAS than a posterior placenta in women with prior CD; the location of the placenta should therefore be evaluated in all women in the second trimester.

Continue to: Lacunae

Lacunae. The finding of multiple hypoechoic vascular spaces within the placental parenchyma has been associated with PAS (FIGURES 3 and 4). The pathogenesis of this finding is probably related to alterations in placental tissue resulting from long-term exposure to pulsatile blood flow.¹¹

Finberg and colleagues introduced a grading system for placental lacunae in 1992 that is still used:

• Grade 0: no lacunae seen
• Grade 1: 1 to 3 lacunae seen
• Grade 2: 4 to 6 lacunae seen
• Grade 3: multiple lacunae seen throughout the placenta.¹²

The sensitivity and specificity of lacunae as an independent marker for PAS have been reported to be 77% and 95%, respectively.¹³ Despite these findings, several studies report a range of sensitivity (73% to 100%) and negative predictive value (88% to 100%).¹⁴ Even in Finberg’s original work, 27% of cases of confirmed PAS had Grade 0 or Grade 1 placental lacunae and 11% of cases of placenta previa, without PAS, demonstrated Grade 2 lacunae.¹² There is agreement, however, that, the more lacunae, the higher the risk of PAS.

Continue to: Other US markers for PAS

Retroplacental–myometrial interface

Loss of the normal hypoechoic (clear) retroplacental zone, also referred to as loss of the clear space between placenta and uterus, is another marker of PAS (FIGURE 5). This finding corresponds to pathologic loss of the decidua basalis as trophoblastic tissue invades directly through the myometrium.¹⁵ This sonographic finding has been reported to have a detection rate of approximately 93%, with sensitivity of 52% and specificity of 57%, for PAS; the false-positive rate, however, has been in the range of 21% or higher. This marker should not be used alone because it is angle-dependent and can be found (as an absent clear zone) in normal anterior placentas.¹⁶

The strength of this US marker is in its negative predictive value, which ranges from 96% to 100%. The presence of a hypoechoic retroplacental clear space that extends the length of the placenta makes PAS unlikely.¹⁷ Of note, the clear zone may appear falsely absent as a result of increased pressure from the US probe.

Retroplacental myometrial thickness

Retroplacental myometrial thickness is difficult to assess because the lower uterine-segment myometrium thins in normal pregnancy as term approaches. This measurement also can be influenced by direct pressure of the US probe and fullness of the maternal bladder.¹⁸ In patients who have had a CD but who do not have PAS, the median myometrial thickness of the lower uterine segment in the third trimester is 2.4 mm.¹⁹

Thinning of the myometrium in the upper uterine segment always should be of concern. Studies of this marker have reported sensitivity of US ranging from 22% to 100% and specificity from 72% to 100%.^9,20 Given such variability, it is important to standardize the gestational age and sonographic approach for this marker.

Continue to: Uterovesical interface

Studies also have reported that abnormalities of the uterovesical interface are predictive of PAS. The uterovesical interface is best evaluated in a sagittal plane containing the lower uterine segment and a partially full bladder in gray-scale and color Doppler US.¹⁵ The normal uterovesical interface appears as a smooth line, without irregularities or increased vascularity on sagittal imaging.

Abnormalities include focal interruption of the hyperechoic bladder wall, bulging of the bladder wall, and increased vascularity, such as varicosities (FIGURES 5, 6, and 7).¹⁵ These findings may be seen as early as the first trimester but are more commonly noted in the second and third trimesters.⁷ The authors of a recent meta-analysis concluded that irregularity of the uterovesical interface is the most specific marker for invasive placentation (99.75% confidence interval; range, 99.5% to 99.9%).¹³

Other US markers and modalities

Three-dimensional US. Studies have evaluated the role of 3-dimensional (3D) US for predicting PAS. Application of 3D US in vascular mode has shown promise because it allows for semiquantitative assessment of placental vasculature.²² Using 3D US to screen for PAS presents drawbacks, however: The technology is not well-standardized and requires significant operator expertise for volume acquisition and manipulation. Prospective studies are needed before 3D US can be applied routinely to screen for and diagnose PAS.

Color Doppler US. As an adjunct to gray-scale US, color Doppler US can be used for making a diagnosis of PAS. Color Doppler US helps differentiate a normal subplacental venous complex with nonpulsatile, low-velocity venous blood flow waveforms from markedly dilated peripheral subplacental vascular channels with pulsatile venous-type flow, which suggests PAS. These vascular channels are often located directly over the cervix. In addition, the observation of bridging vessels linking the placenta and bladder with high diastolic arterial blood flow also suggests invasion.²¹ In a meta-analysis, overall sensitivity of color Doppler US for the diagnosis of PAS was 91%, with specificity of 87%.¹³

The value of utilizing multiple markers

The accuracy of US diagnosis of PAS is likely improved by using more than 1 sonographic marker. Pilloni and colleagues,²⁰ in a prospective analysis, found that 81% of cases of confirmed PAS had ≥2 markers and 51% of cases had ≥3 markers.

Several scoring systems have been proposed for making the diagnosis of PAS using combinations of sonographic markers, placental location, and clinical history.^19,24,25 In 2016, Tovbin and colleagues,²⁵ in a prospective study, evaluated a scoring system that included:

• number of previous CDs
• number of, maximum dimension of, and presence of blood flow in lacunae
• loss of uteroplacental clear zone
• placental location
• hypervascularity of the uterovesical or uteroplacental interface.

Tovbin assigned 1 or 2 points to each criterion. Each sonographic marker was found to be significantly associated with PAS when compared to a high-risk control group. A score of ≥8 was considered “at high risk” and predicted 69% of PAS cases.

Regrettably, no combination of US markers reliably predicts the depth of invasion of the placenta.²⁶

Continue to: A standardized approach is needed

To decrease variability and improve the US diagnosis of PAS, it is important to define and standardize the diagnosis of each sonographic marker for PAS.⁴ In 2016, the European Working Group on Abnormally Invasive Placenta (EW-AIP) proposed a set of US markers that always should be reported when performing an US examination for suspected abnormal placentation (TABLE).²³ Despite this effort by the EW-AIP, ambiguity remains over sonographic definitions of several PAS markers. For example, what determines a placental lacuna on US? And what constitutes an abnormal uterovesical interface? There is a need for a more objective definition of US markers of PAS and a standardized approach to the US examination in at-risk pregnancies.

The Society for Maternal-Fetal Medicine is coordinating a multi-society task force to address the need to define and standardize the US diagnosis of PAS.

Observations on other PAS diagnostic modalities

Magnetic resonance imaging

Adjunctive role. Magnetic resonance imaging (MRI) is often used as an adjunctive diagnostic modality in cases of suspected PAS. Several markers for PAS have been described on MRI, including¹⁵:

• intraplacental T2-weighted dark bands
• abnormal intraplacental vascularity
• heterogeneous intraplacental signal intensity
• focal interruption of the myometrium by the placenta
• uterine bulging.

Based on a recent meta-analysis, overall sensitivity of MRI for detecting PAS is 86% to 95%, with specificity of 80% to 95%. Although this is comparable to the sensitivity and specificity of US,²⁷ studies of MRI in PAS are smaller and more prone to bias than in studies of US, because MRI typically is used only in patients at highest risk for PAS. Few studies comparing US to MRI for PAS have been performed; all are small and lack statistical power.

Complementary role. MRI can be complementary to US in cases in which the placenta is posterior or located laterally²⁸ but, importantly, rarely changes decisions about surgical management when used in conjunction with US to assess patients for the diagnosis of PAS. (An exception might lie in the ability of MRI to assess the degree or depth of invasion of the placenta and discerning placenta percreta from placenta accreta.¹⁵)

Enhancement with contrast. Addition of gadolinium-based contrast might improve the ability of MRI to make a diagnosis of PAS, but gadolinium crosses the placenta barrier. Although fetal effects of gadolinium have not been observed, American College of Radiology guidelines recommend avoiding this contrast agent during pregnancy unless absolutely essential.²⁹

Specific indications. MRI without contrast should be considered 1) when US is inconclusive and 2) to further evaluate a posterior placenta suspicious for invasion, to define the precise topography of extrauterine placental invasion. The additional information offered by MRI might alter surgical planning.¹⁵

Biomarkers

Multiple serum biomarkers have been proposed to predict PAS in high-risk women. PAS might be associated with increased levels of first-trimester pregnancy-associated plasma protein A, second-trimester maternal serum alpha fetoprotein, and human chorionic gonadotropin, but studies of the utility of these biomarkers have yielded contradictory results.^30,31 Biomarkers are of interest and have significant clinical applicability, but none of the ones identified to date have high sensitivity or specificity for predicting PAS prenatally. Research is ongoing to identify markers of PAS that have sufficient predictive power.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Placenta accreta spectrum (PAS) describes abnormal invasion of placental tissue into or through the myometrium, comprising 3 distinct conditions: placenta accreta, placenta increta, and placenta percreta. This complication is relatively new to obstetrics, first described in 1937.¹

The overall incidence of PAS has been increasing over several decades, in parallel to an increasing rate of cesarean delivery (CD), with an incidence from 1982 through 2002 of 1 in 533 pregnancies, representing a 5-fold increase since the 1980s.² PAS is associated with significant morbidity and mortality, including fetal growth restriction, preterm delivery, placental abruption antenatally, and hemorrhage during delivery or postpartum.

Prenatal diagnosis of PAS and planned delivery at an experienced center are associated with significant reduction in maternal and fetal morbidity.³ In an era of advanced imaging modalities, prenatal detection of PAS regrettably remains variable and largely subjective: As many as 20% to 50% of cases of PAS escape prenatal diagnosis.^3,4

In this article, we review the sonographic markers of PAS, including diagnostic accuracy, and propose a standardized approach to prenatal diagnosis. Throughout our discussion, we describe protocols for detection of PAS practiced at our Maternal-Fetal Medicine Program in the Department of Obstetrics and Gynecology, Eastern Virginia Medical School (also see “US evaluation of PAS risk: The authors’ recommended approach”).

Numerous risk factors

There are many risk factors for PAS, including prior uterine surgery or instrumentation, such as CD, uterine curettage, myomectomy, pelvic radiation, and endometrial ablation. Other risk factors include smoking, in vitro fertilization, advanced maternal age, multiparity, and a brief interval between prior CD and subsequent pregnancy.⁵ Of major significance is the increased risk of PAS in the presence of placenta previa with prior CD.⁶ Knowledge of clinical risk factors by the interpreting physician appears to be associated with improved detection of PAS on ultrasonography (US).⁴

Ultrasonographic markers of PAS

First-trimester markers

Sonographic markers of PAS in the first trimester include:

• a gestational sac implanted in the lower uterine segment or in a CD scar
• multiple hypoechoic spaces within the placenta (lacunae).⁷

Lower uterine-segment implantation has been defined by Ballas and colleagues as 1) a gestational sac implanted in the lower one-third of the uterus between 8 and 10 weeks’ gestation or 2) a gestational sac occupying primarily the lower uterine segment from 10 weeks’ gestation onward (FIGURE 1).⁸ Our experience is that it is difficult to accurately assess lower uterine-segment implantation beyond 13 weeks of gestation because the sac typically expands to fill the upper uterine cavity.

Continue to: Color Doppler US...

Color Doppler US can help differentiate lower uterine-segment implantation from a gestational sac of a failed pregnancy in the process of expulsion by demonstrating loss of circumferential blood flow in the failed pregnancy. Furthermore, applying pressure to the anterior surface of the uterus will result in downward movement of the gestational sac of a failed pregnancy.⁹

Not all gestational sacs that implant in the lower uterine segment lead to PAS: Subsequent normal pregnancies have been reported in this circumstance. In such cases, a normal thick myometrium is noted anterior to the gestational sac.⁷ A patient with lower uterine-segment implantation without evidence of anterior myometrial thinning remains at risk for third-trimester placenta previa.⁷

Cesarean scar pregnancy carries significant risk of PAS. In these cases, the gestational sac is typically implanted within the scar, resulting in a thin anterior myometrium and significantly increased vascularity of the placental–myometrial and bladder–uterine wall interfaces (FIGURE 2).⁹ Differentiating cesarean scar pregnancy from a lower uterine-segment implantation is easier to perform before the eighth week of gestation but becomes more difficult as pregnancy advances. Although it might be useful to distinguish between true cesarean scar pregnancy and lower uterine-segment implantation adjacent to or involving the scar, both carry considerable risk of PAS and excessive hemorrhage, and the approach to treating both conditions is quite similar.

Lacunae, with or without documented blood flow on color Doppler US, are the third marker of PAS in the first trimester.⁸ Although some retrospective series and case reports describe the finding of lacunae in the first trimester of patients with diagnosed PAS, more recent literature suggests that these spaces are seen infrequently and at a similar frequency in women with and without PAS at delivery.⁷

Second- and third-trimester markers

Multiple diagnostic sonographic markers of PAS have been described in the second and third trimesters.

Placental location is a significant risk factor for PAS. Placenta previa in the setting of prior CD carries the highest risk of PAS—as high as 61% in women with both placenta previa and a history of 3 CDs.¹⁰ An anterior placenta appears to be a stronger risk factor for PAS than a posterior placenta in women with prior CD; the location of the placenta should therefore be evaluated in all women in the second trimester.

Continue to: Lacunae

Lacunae. The finding of multiple hypoechoic vascular spaces within the placental parenchyma has been associated with PAS (FIGURES 3 and 4). The pathogenesis of this finding is probably related to alterations in placental tissue resulting from long-term exposure to pulsatile blood flow.¹¹

Finberg and colleagues introduced a grading system for placental lacunae in 1992 that is still used:

• Grade 0: no lacunae seen
• Grade 1: 1 to 3 lacunae seen
• Grade 2: 4 to 6 lacunae seen
• Grade 3: multiple lacunae seen throughout the placenta.¹²

The sensitivity and specificity of lacunae as an independent marker for PAS have been reported to be 77% and 95%, respectively.¹³ Despite these findings, several studies report a range of sensitivity (73% to 100%) and negative predictive value (88% to 100%).¹⁴ Even in Finberg’s original work, 27% of cases of confirmed PAS had Grade 0 or Grade 1 placental lacunae and 11% of cases of placenta previa, without PAS, demonstrated Grade 2 lacunae.¹² There is agreement, however, that, the more lacunae, the higher the risk of PAS.

Continue to: Other US markers for PAS

Retroplacental–myometrial interface

Loss of the normal hypoechoic (clear) retroplacental zone, also referred to as loss of the clear space between placenta and uterus, is another marker of PAS (FIGURE 5). This finding corresponds to pathologic loss of the decidua basalis as trophoblastic tissue invades directly through the myometrium.¹⁵ This sonographic finding has been reported to have a detection rate of approximately 93%, with sensitivity of 52% and specificity of 57%, for PAS; the false-positive rate, however, has been in the range of 21% or higher. This marker should not be used alone because it is angle-dependent and can be found (as an absent clear zone) in normal anterior placentas.¹⁶

The strength of this US marker is in its negative predictive value, which ranges from 96% to 100%. The presence of a hypoechoic retroplacental clear space that extends the length of the placenta makes PAS unlikely.¹⁷ Of note, the clear zone may appear falsely absent as a result of increased pressure from the US probe.

Retroplacental myometrial thickness

Retroplacental myometrial thickness is difficult to assess because the lower uterine-segment myometrium thins in normal pregnancy as term approaches. This measurement also can be influenced by direct pressure of the US probe and fullness of the maternal bladder.¹⁸ In patients who have had a CD but who do not have PAS, the median myometrial thickness of the lower uterine segment in the third trimester is 2.4 mm.¹⁹

Thinning of the myometrium in the upper uterine segment always should be of concern. Studies of this marker have reported sensitivity of US ranging from 22% to 100% and specificity from 72% to 100%.^9,20 Given such variability, it is important to standardize the gestational age and sonographic approach for this marker.

Continue to: Uterovesical interface

Studies also have reported that abnormalities of the uterovesical interface are predictive of PAS. The uterovesical interface is best evaluated in a sagittal plane containing the lower uterine segment and a partially full bladder in gray-scale and color Doppler US.¹⁵ The normal uterovesical interface appears as a smooth line, without irregularities or increased vascularity on sagittal imaging.

Abnormalities include focal interruption of the hyperechoic bladder wall, bulging of the bladder wall, and increased vascularity, such as varicosities (FIGURES 5, 6, and 7).¹⁵ These findings may be seen as early as the first trimester but are more commonly noted in the second and third trimesters.⁷ The authors of a recent meta-analysis concluded that irregularity of the uterovesical interface is the most specific marker for invasive placentation (99.75% confidence interval; range, 99.5% to 99.9%).¹³

Other US markers and modalities

Three-dimensional US. Studies have evaluated the role of 3-dimensional (3D) US for predicting PAS. Application of 3D US in vascular mode has shown promise because it allows for semiquantitative assessment of placental vasculature.²² Using 3D US to screen for PAS presents drawbacks, however: The technology is not well-standardized and requires significant operator expertise for volume acquisition and manipulation. Prospective studies are needed before 3D US can be applied routinely to screen for and diagnose PAS.

Color Doppler US. As an adjunct to gray-scale US, color Doppler US can be used for making a diagnosis of PAS. Color Doppler US helps differentiate a normal subplacental venous complex with nonpulsatile, low-velocity venous blood flow waveforms from markedly dilated peripheral subplacental vascular channels with pulsatile venous-type flow, which suggests PAS. These vascular channels are often located directly over the cervix. In addition, the observation of bridging vessels linking the placenta and bladder with high diastolic arterial blood flow also suggests invasion.²¹ In a meta-analysis, overall sensitivity of color Doppler US for the diagnosis of PAS was 91%, with specificity of 87%.¹³

The value of utilizing multiple markers

The accuracy of US diagnosis of PAS is likely improved by using more than 1 sonographic marker. Pilloni and colleagues,²⁰ in a prospective analysis, found that 81% of cases of confirmed PAS had ≥2 markers and 51% of cases had ≥3 markers.

Several scoring systems have been proposed for making the diagnosis of PAS using combinations of sonographic markers, placental location, and clinical history.^19,24,25 In 2016, Tovbin and colleagues,²⁵ in a prospective study, evaluated a scoring system that included:

• number of previous CDs
• number of, maximum dimension of, and presence of blood flow in lacunae
• loss of uteroplacental clear zone
• placental location
• hypervascularity of the uterovesical or uteroplacental interface.

Tovbin assigned 1 or 2 points to each criterion. Each sonographic marker was found to be significantly associated with PAS when compared to a high-risk control group. A score of ≥8 was considered “at high risk” and predicted 69% of PAS cases.

Regrettably, no combination of US markers reliably predicts the depth of invasion of the placenta.²⁶

Continue to: A standardized approach is needed

To decrease variability and improve the US diagnosis of PAS, it is important to define and standardize the diagnosis of each sonographic marker for PAS.⁴ In 2016, the European Working Group on Abnormally Invasive Placenta (EW-AIP) proposed a set of US markers that always should be reported when performing an US examination for suspected abnormal placentation (TABLE).²³ Despite this effort by the EW-AIP, ambiguity remains over sonographic definitions of several PAS markers. For example, what determines a placental lacuna on US? And what constitutes an abnormal uterovesical interface? There is a need for a more objective definition of US markers of PAS and a standardized approach to the US examination in at-risk pregnancies.

The Society for Maternal-Fetal Medicine is coordinating a multi-society task force to address the need to define and standardize the US diagnosis of PAS.

Observations on other PAS diagnostic modalities

Magnetic resonance imaging

Adjunctive role. Magnetic resonance imaging (MRI) is often used as an adjunctive diagnostic modality in cases of suspected PAS. Several markers for PAS have been described on MRI, including¹⁵:

• intraplacental T2-weighted dark bands
• abnormal intraplacental vascularity
• heterogeneous intraplacental signal intensity
• focal interruption of the myometrium by the placenta
• uterine bulging.

Based on a recent meta-analysis, overall sensitivity of MRI for detecting PAS is 86% to 95%, with specificity of 80% to 95%. Although this is comparable to the sensitivity and specificity of US,²⁷ studies of MRI in PAS are smaller and more prone to bias than in studies of US, because MRI typically is used only in patients at highest risk for PAS. Few studies comparing US to MRI for PAS have been performed; all are small and lack statistical power.

Complementary role. MRI can be complementary to US in cases in which the placenta is posterior or located laterally²⁸ but, importantly, rarely changes decisions about surgical management when used in conjunction with US to assess patients for the diagnosis of PAS. (An exception might lie in the ability of MRI to assess the degree or depth of invasion of the placenta and discerning placenta percreta from placenta accreta.¹⁵)

Enhancement with contrast. Addition of gadolinium-based contrast might improve the ability of MRI to make a diagnosis of PAS, but gadolinium crosses the placenta barrier. Although fetal effects of gadolinium have not been observed, American College of Radiology guidelines recommend avoiding this contrast agent during pregnancy unless absolutely essential.²⁹

Specific indications. MRI without contrast should be considered 1) when US is inconclusive and 2) to further evaluate a posterior placenta suspicious for invasion, to define the precise topography of extrauterine placental invasion. The additional information offered by MRI might alter surgical planning.¹⁵

Biomarkers

Multiple serum biomarkers have been proposed to predict PAS in high-risk women. PAS might be associated with increased levels of first-trimester pregnancy-associated plasma protein A, second-trimester maternal serum alpha fetoprotein, and human chorionic gonadotropin, but studies of the utility of these biomarkers have yielded contradictory results.^30,31 Biomarkers are of interest and have significant clinical applicability, but none of the ones identified to date have high sensitivity or specificity for predicting PAS prenatally. Research is ongoing to identify markers of PAS that have sufficient predictive power.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

The American College of Obstetricians and Gynecologists (ACOG) and specifically the Junior Fellow College Advisory Council (JFCAC) are rolling out steps to help you make your voice heard. Starting October 1, head to acog.org/advocacy to check out the ACOG Physician Advocacy video to get inspired. (Or watch it here!) Whether you are a seasoned advocate or just getting started, ACOG and women across the country are counting on you!

Week 1 (October 1–7): Why I advocate

The focus of this week is on delving into topics that interest you, learning why advocacy is critically important, and developing your own message to advocate for women’s health.

• View advocacy videos here to understand what advocacy is and why it is so important.
• See ACOG’s 2018 list of legislative priorities here to find topics that inspire you.

Week 2 (October 8–14): Use your voice

Explore the multitude of platforms available today for amplifying your message. Learn to use social media smartly, get advice for how to write op-eds for local outlets, add your name to support current legislative efforts, and find out who your representatives are to schedule sit-down meetings.

• For tips on communicating with elected officials, click here.
• Connect with ACOG and your district on social media, and remember to use social media responsibly to advocate effectively. See this link for more information!
• Don’t forget to include #JFadvoMonth in your posts while highlighting your advocacy work on social media!

Continued to: Week 3 (October 15–19): Empower your patients

As a physician, advocating for your patient extends into the clinic itself. Access toolkits, patient websites, handouts, and resources available through ACOG.

• Familiarize yourself with the Patient Page for videos, infographics, and FAQs that are useful resources for your patients.
• Toolkits for providers are available here—use these to enhance your practice and empower your patients!

Week 4 (October 22–28): Take it forward

Advocacy happens year-round. Be sure you are actively involved in ACOG’s efforts. Participate in calls to action and remember on November 6 to GET OUT THE VOTE!

• Participate in the annual Congressional Leadership Conference (March 10–12, 2019) in Washington, DC. Descend on Washington with hundreds of fellow ObGyns to advocate to Congress on important issues. For more information, click here.
• Donate to the Ob-GynPAC, ACOG’s political action committee dedicated to electing officials who support our specialty.
• Run for office! ACOG has resources to support you. Be on the lookout for opportunities to attend candidate workshops sponsored by the Ob-GynPAC!

Get active now!

We are at a critical moment for women’s health and the future of our specialty. Key issues nationally include advocating to Congress to move forward with bills in the Senate (S 1112) and House (HR 1318) to support efforts to reduce maternal mortality. (See this article for background information on these bills.)

To find your elected officials and take action now, click here and tell Congress to help prevent maternal mortality, defend patient protections, and improve access and quality of maternity care.

You can be an advocate for your patients and your profession. Your voice matters. Now is the time to be heard.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

The American College of Obstetricians and Gynecologists (ACOG) and specifically the Junior Fellow College Advisory Council (JFCAC) are rolling out steps to help you make your voice heard. Starting October 1, head to acog.org/advocacy to check out the ACOG Physician Advocacy video to get inspired. (Or watch it here!) Whether you are a seasoned advocate or just getting started, ACOG and women across the country are counting on you!

Week 1 (October 1–7): Why I advocate

The focus of this week is on delving into topics that interest you, learning why advocacy is critically important, and developing your own message to advocate for women’s health.

• View advocacy videos here to understand what advocacy is and why it is so important.
• See ACOG’s 2018 list of legislative priorities here to find topics that inspire you.

Week 2 (October 8–14): Use your voice

Explore the multitude of platforms available today for amplifying your message. Learn to use social media smartly, get advice for how to write op-eds for local outlets, add your name to support current legislative efforts, and find out who your representatives are to schedule sit-down meetings.

• For tips on communicating with elected officials, click here.
• Connect with ACOG and your district on social media, and remember to use social media responsibly to advocate effectively. See this link for more information!
• Don’t forget to include #JFadvoMonth in your posts while highlighting your advocacy work on social media!