T-shaped uterus and subtle uterine variances

A need for reliable criteria, Fertility and Sterility, August 2019


The ASRM Class VII, the ESHRE/ESGE Class U1, and the T-shaped uterus have a uniquely interesting history. The T-shaped uterus was first described as a diethylstilbestrol– (DES-) related congenital uterine anomaly based on findings from hysterosalpingography by Kaufman in 1977. Together with two similar morphologic forms of the uterus—constricting bands in the uterine cavity and a widening of the lower two-thirds of the uterus—this was included as a separate class of DES-related anomalies by the Buttram and Gibbons 1979 classification, and its further modification—the American Fertility Society classification.

In 2013, ESHRE/ESGE singled out a subtle uterine variance with a thickened lateral wall and a T-shaped uterus. As a result, the diagnosis of subtle uterine variances has increased with the designation of a T-shaped uterus or dysmorphic uterus and surgical repair is offered to enhance fertility. However, there is insufficient evidence to offer it in daily practice even in women with recurrent pregnancy loss, where historically metroplasty of the T-shaped uterus is rarely reported and its surgical correction is always questionable.

In this issue Alonso Pacheco et al. present a nicely done video using three-dimensional ultrasound and hysteroscopy in three cases of what they believe is a T-shaped uterus that is representative in distinguishing three of its subclasses. The authors used three-dimensional ultrasound and hysteroscopy to suggest that T-shaped uterus can be subclassified as T-shaped, Y-shaped, or I-shaped uterus. However, the division still remains arbitrary based on subjective impression of the presence of thickened wall and letter-shaped uterine cavities in these conditions. Discussion.

Uterus transplantation is still highly experimental in 2018, ASRM committee says

American Society for Reproductive Medicine position statement on uterus transplantation: a committee opinion

Following the birth of the first child from a transplanted uterus in Gothenburg, Sweden, in 2014, other centers worldwide have produced scientific reports of successful uterus transplantation, as well as more recent media reports of successful births.

The American Society for Reproductive Medicine recognizes uterus transplantation as the first successful medical treatment of absolute uterus factor infertility, while cautioning health professionals, patient advocacy groups, and the public about its highly experimental nature.

Read American Society for Reproductive Medicine position statement on uterus transplantation: a committee opinion on Fertility and Sterility, September 2018.

Sadly for many DES daughters having their own children is not possible! Many of us who have experienced miscarriages, want to have kids but are struggling or unable to… Find out more about DES pregnancy risks and DES studies on fertility and pregnancy.

Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy

The Practice Committee of the American Society for Reproductive Medicine Opinion, 2018

“Patients preparing to undergo gonadotoxic medical therapy or radiation therapy or gonadectomy should be provided with prompt counseling regarding available options for fertility preservation. Fertility preservation can best be provided by comprehensive programs designed and equipped to confront the unique challenges facing these patients.

Over 100,000 individuals less than 45 years of age are diagnosed with cancer annually in the United States. Over the past 4 decades, advancements in cancer therapies, particularly chemotherapeutics, have led to dramatic improvements in survival. Given the reproductive risks of cancer therapies and improved long-term survival, there has been growing interest in expanding the reproductive options for cancer patients. Indeed, both cancer survivors and the medical community have acknowledged the importance of patient counseling” …

continue reading on the American Society for Reproductive Medicine practice guidelines.

Endometriosis and pregnancy outcome : women with previously excised posterior DIE

Obstetric complications after laparoscopic excision of posterior deep infiltrating endometriosis: a case–control study

2018 Study Abstract

In this issue, Nirgianakis et al. present a retrospective analysis of the complications of pregnancy after laparoscopic excision of deep infiltrating endometriosis (DIE). Most important is that excision of DIE does not affect the increased risk of placenta previa, gestational hypertension, and intrauterine growth retardation (IUGR) associated with endometriosis. In addition, the risk of a vaginal delivery was not increased in the entire group or in the 26 women with a vaginal excision of endometriosis.

Read the full text (free access).
Fertility and Sterility, Volume 110, Issue 3, Pages 406–407, August 2018.

DES Exposure and Endometriosis

The impact of assisted reproductive technology on the offspring

Association of birth defects with the mode of assisted reproductive technology in a Chinese data-linkage cohort

2018 Study Abstract

To evaluate the impact of assisted reproductive technology (ART) on the offspring of Chinese population.

Retrospective, data-linkage cohort.

Not applicable.

Live births resulting from ART or natural conception.


Main Outcome Measure(s)
Birth defects coded according to ICD-10.

Births after ART were more likely to be female and multiple births, especially after intracytoplasmic sperm injection (ICSI). ART was associated with a significantly increased risk of birth defects, especially, among singleton births, a significantly increased risk in fresh-embryo cycles after in vitro fertilization (IVF) and frozen-embryo cycles after ICSI. Associations between ART and multiple defects, between ART and gastrointestinal malformation, genital organs malformation, and musculoskeletal malformation among singleton births, and between ART and cardiac septa malformation among multiple births were observed.

This study suggests that ART increases the risk of birth defects. Subgroup analyses indicate higher risk for both fresh and frozen embryos, although nonsignificantly for frozen embryos after IVF and for fresh embryos were presented with low power. Larger sample size research is needed to clarify effects from fresh- or frozen-embryo cycles after IVF and ICSI.

Maternal antidepressant use associated with increased risk of miscarriage

Major depression, antidepressant use, and male and female fertility : Cohort study

2018 Study Abstract

To determine if maternal major depression (MD), antidepressant use, or paternal MD are associated with pregnancy outcomes after non-IVF fertility treatments.

Cohort study, DOI: https://doi.org/10.1016/j.fertnstert.2018.01.029, May 2018.


Participants in two randomized trials: PPCOS II (clomiphene citrate versus letrozole for polycystic ovary syndrome), and AMIGOS (gonadotropins versus clomiphene citrate versus letrozole for unexplained infertility).

Female and male partners completed the Patient Health Questionnaire (PHQ-9). Female medication use was collected. PHQ-9 score ≥10 was used to define currently active MD.

Main Outcome Measure(s)
Primary outcome: live birth. Secondary outcomes: pregnancy, first-trimester miscarriage. Poisson regression models were used to determine relative risks after adjusting for age, race, income, months trying to conceive, smoking, and study (PPCOS II versus AMIGOS).

Data for 1,650 women and 1,608 men were included. Among women not using an antidepressant, the presence of currently active MD was not associated with poorer fertility outcomes (live birth, miscarriage), but rather was associated with a slightly increased likelihood of pregnancy. Maternal antidepressant use (n = 90) was associated with increased risk of miscarriage, and male partners with currently active MD were less likely to achieve conception.

Currently active MD in the female partner does not negatively affect non-IVF treatment outcomes; however, currently active MD in the male partner may lower the likelihood of pregnancy. Maternal antidepressant use is associated with first-trimester pregnancy loss, which may depend upon the type of antidepressant.

IVF success : the importance of characterizing optimal embryo transfer technique

Live birth rate following embryo transfer is significantly influenced by the physician performing the transfer: data from 2707 euploid blastocyst transfers by 11 physicians

Pregnancy and live birth rates obtained after in vitro fertilization (IVF) are highly variable depending on the practitioner who performs the embryo transfer, regardless of the number of transfers performed per practitioner and years of practice, according to a US study presented in 2016 at the American Society for Reproductive Medicine (ASRM) conference in Salt Lake City.

2016 Study Abstract

Multiple prior studies have demonstrated variation in IVF success rates according the provider performing the embryo transfer procedure. However, these studies were limited by lack of control for embryonic aneuploidy and evaluation of cleavage stage transfers only. Thus, our objective was to isolate the contribution of physician variability on the chance of embryo transfer (ET) success in contemporary ART by evaluating euploid blastocyst transfers in a single practice setting.

Retrospective cohort.

Materials and Methods
All euploid blastocyst transfers from 2011 to 2015 were evaluated. The physician performing the ET, maternal age, blastocyst grade, and information regarding fresh versus frozen transfer were recorded. During the study period, 11 physicians were randomly assigned to be “ET physician of the day” in a rotating fashion. To avoid selection bias, all transfers not performed by the assigned “physician of the day” were excluded to assure that the randomness provided by the rotating schedule remained intact. Analysis was performed using chi-squared tests.

There were 2707 euploid ETs performed that met inclusion criteria. The mean number of transfers per physician was 246. There was no difference in maternal age, blastocyst grade, or proportion of fresh vs. frozen transfers among the physicians. The implantation rate (IR), clinical pregnancy rate (CPR), and live birth rate (LBR) differed significantly between worst performing and best performing physicians. When compared to worst performer, an additional live birth could be expected for every 6 ETs performed by the best performer. There was no association between success rates and number of ETs performed by provider during the study period or number of years elapsed since completion of training.

When controlling for embryonic factors by utilizing euploid blastocyst transfers, live birth rate is still strongly influenced by the physician performing the transfer procedure. Given that these data only include ETs in which patients were randomly assigned to a given provider, the impact of the physician factor on success rates is truly isolated. These findings highlight the importance of characterizing optimal ET technique and present an opportunity for improving success rates through remediation of experienced providers and formalized instruction of trainees.


Can in vitro fertilisation increase the risk for preeclampsia ?

Embryo cryopreservation and preeclampsia risk

Pre-eclampsia is a disorder of pregnancy that increases the risk of poor outcomes for both the mother and the baby.

2017 Study Abstract

To determine whether assisted reproductive technology (ART) cycles involving cryopreserved-warmed embryos are associated with the development of preeclampsia.

Retrospective cohort study.

IVF clinics and hospitals.

A total of 15,937 births from ART: 9,417 singleton and 6,520 twin.

We used linked ART surveillance, birth certificate, and maternal hospitalization discharge data, considering resident singleton and twin births from autologous or donor eggs from 2005–2010.

Main Outcome Measure(s)
We compared the frequency of preeclampsia diagnosis for cryopreserved-warmed versus fresh ET and used multivariable logistic regression to adjust for confounders.

Among pregnancies conceived with autologous eggs resulting in singletons, preeclampsia was greater after cryopreserved-warmed versus fresh ET (7.51% vs. 4.29%, adjusted odds ratio = 2.17 [95% CI 1.67–2.82]). Preeclampsia without and with severe features, preeclampsia with preterm delivery, and chronic hypertension with superimposed preeclampsia were more frequent after cryopreserved-warmed versus fresh ET (3.99% vs. 2.55%; 2.95% vs. 1.41%; 2.76 vs. 1.48%; and 0.95% vs. 0.43%, respectively). Among pregnancies from autologous eggs resulting in twins, the frequency of preeclampsia with severe features (9.26% vs. 5.70%) and preeclampsia with preterm delivery (14.81% vs. 11.74%) was higher after cryopreserved versus fresh transfers. Among donor egg pregnancies, rates of preeclampsia did not differ significantly between cryopreserved-warmed and fresh ET (10.78% vs. 12.13% for singletons and 28.0% vs. 25.15% for twins).

Among ART pregnancies conceived using autologous eggs resulting in live births, those involving transfer of cryopreserved-warmed embryos, as compared with fresh ETs, had increased risk for preeclampsia with severe features and preeclampsia with preterm delivery.


IVF treatment : a healthy singleton delivery is best achieved by SET

Single-embryo transfer point – it is the way forward

In vitro fertilization (IVF) treatment in the United States is complicated by a high rate of multiple-gestation pregnancies. In 2014, the Society for Assisted Reproductive Technology reported that 23% of women <38 years of age with a pregnancy from their IVF treatment had a twin-gestation pregnancy. Although this is an improvement over past years, it remains an unacceptably high rate of twins, considering the medical risks and financial burdens associated with such pregnancies.

In this issue of Fertility and Sterility, Mersereau et al. have added strong support to the conclusion that single-embryo transfer (SET) is highly effective at reducing multiple-gestation birth rates: a 47% decrease with the use of SET compared with double-embryo transfer (DET). Furthermore, using data from their study and others, Mersereau’s team has led a revision of American Society for Reproductive Medicine committee opinion guidelines to unambiguously call for SET for women under the age of 38 years with a favorable prognosis for pregnancy. With the increasing weight of evidence and explicit professional guidelines, why is DET still so common in the United States?

In their article, Mersereau et al. report a comprehensive analysis of 10 years of national SET data, finding a 10%–15% reduction in live birth rate (LBR) with the use of SET. This reduction is not attractive to either physicians or patients, for whom IVF pregnancy rates matter a great deal. Indeed, we have shown that, despite education about the risks of twins after DET, most patients would still choose this option over SET, even with as little as a 10% drop in the LBR.

Yet we think that the 10%–15% difference in LBR may be an overestimate of the negative effect of SET on LBR, considering trends in current clinical IVF care. As reported, blastocyst transfers are becoming increasingly common, and SET live birth rates are higher with blastocysts than with cleavage-stage embryo. In fact, the LBR differences between DET and SET were still reduced, but only in the 6%–8% range, when looking at fresh blastocyst transfers in a first or second cycle. Even this may be an overestimate of the true difference between DET and SET, because higher pregnancy rates are seen when the single transferred embryo comes from a larger cohort of available embryos.

Thus, it is likely a false comparison to judge the success of SET with one or more embryos cryopreserved (at least two embryos in the cohort) against DET with one or more embryos cryopreserved (at least 3 embryos in the cohort). In a recent analysis of national IVF outcomes data, we strictly controlled for the size of the available cohort and found very similar pregnancy rates in younger good-prognosis patients undergoing elective SET versus DET on day 5–6.

We think that this trend of increasing blastocyst transfers combined with improvements in embryo selection techniques (such as preimplantation genetic screening) will result in further increases in SET pregnancy rates and allow clinics to more confidently offer SET with little to no impact on their clinic-specific pregnancy outcome. Despite continuing technical advances, however, it is likely that small but potentially significant LBR differences will persist between SET and DET if as a field we continue to report and emphasize pregnancy rates per transfer instead of cumulative pregnancy rates per fresh IVF cycle. As mentioned in Mersereau et al.’s paper, predictive models suggest that cumulative LBRs with the use of sequential SET are equal or superior to DET.

Further studies confirming this prediction will help to convince physicians, patients, and insurance providers of the benefits and feasibility of SET, even if this strategy requires additional transfers and a slightly longer time to pregnancy. A healthy singleton delivery should be the goal of all IVF cycles, and this is best achieved by SET.

Do we need to choose between improved sperm selection or efficacy ?

The latest attempt to improve the sperm’s path

Our goal in the in vitro fertilization laboratory is to maximize the ratio between the number of oocytes retrieved and the production of highly viable embryos. We receive the raw material from our patients (oocytes and sperm cells) and, with our knowledge and the available technologies; we try to improve our success rates day by day. One of our endpoints should be the objective application of validated, repeatable, and non-biased therapies and technologies. Few options remain available for oocytes as all the oocytes will be treated to achieve fertilization. In the case of sperm, millions of cells are available to us, but only a few of them will be used. Is there room to improve the sperm’s path? We must move away from the classical methods of sperm selection (swim up or gradients) and pursue any kind of technology that may take into consideration their molecular characteristics, which are related to successful fertilization, embryo development, and live birth.”…

…continue reading What else can we do? The latest attempt to improve the sperm’s path on Fertility and Sterility, Volume 108, Issue 3, Pages 444–445, September 2017.