Rani Fritz - Academia.edu (original) (raw)

Papers by Rani Fritz

Research paper thumbnail of In Vitro Fertilization vs Intracytoplasmic Sperm Injection for Non-Male Factor Preimplantation Genetic Testing-Aneuploidy Cycles: Are There Differences in Embryos Suitable for Transfer Pregnancy Outcomes? A Sart Cors Analysis

Research paper thumbnail of Elevated estradiol (E2) levels in artificial autologous frozen embryo transfer (FET) cycles negatively impact live birth (lb) and ongoing pregnancy (OP) rates

Research paper thumbnail of Dissociation of Pubertal Development Abnormality and Gonadal Dysfunction in Childhood Cancer Survivors

Journal of Adolescent and Young Adult Oncology

Purpose: To determine the relationship between pubertal development and postpubertal gonadal func... more Purpose: To determine the relationship between pubertal development and postpubertal gonadal function in childhood cancer survivors. Methods: Childhood cancer survivors (q10 years of age) who received follow-up care in a pediatric oncology group in an academic medical center during the period from January 1, 1985, to July 1, 2010 were included in this case series. Their pubertal development and gonadal function were evaluated. Results: The cohort consists of 39 males (age 10-21 years) and 35 females (age 10-29 years) with a variety of cancer diagnosis and treatments. The average age at diagnosis was *7.5 years. The average age at the time of the study was 16 and 16.7 years in males and females, respectively, representing a mean follow-up interval of *9 years. Despite the fact that 60% of survivors received cyclophosphamide equivalents and 16.2% received cranial radiation or brain tumor resection, the majority of survivors (68%) presented with both normal puberty and normal gonadal functions at the time of follow-up. In 27% of survivors, puberty development did not predict gonadal function in early adulthood: 20% of survivors had normal puberty, but abnormal gonadal function; 7% of survivors had abnormal puberty, but gonadal function remained normal as young adults. Conclusions: Most childhood cancer survivors had normal puberty and gonadal function despite a variety of cancer treatment modalities. However, normal puberty did not predict normal gonadal function later in life in many survivors. Therefore, close follow-up with gonadal function in adolescent and early adulthood years is essential.

Research paper thumbnail of Identification and characterization of RSIY-11, a novel seminal peptide derived from semenogelin-1, which acts as a neutral endopeptidase inhibitor modulating sperm motility

Journal of Assisted Reproduction and Genetics

Research paper thumbnail of Reproductive aging and elective fertility preservation

Journal of Ovarian Research

Reproductive aging is a natural process that occurs in all women, eventually leading to reproduct... more Reproductive aging is a natural process that occurs in all women, eventually leading to reproductive senescence and menopause. Over the past half century there has been a trend towards delayed motherhood. Postponing reproduction can increase the chance of a woman remaining involuntarily childless as well as an increase in pregnancy complications in those that do achieve pregnancy at advanced maternal age. Despite the well-documented decrease in fecundity that occurs as a woman ages, reproductive aged women frequently overestimate the age at which a significant decline in fertility occurs and overestimate the success of assisted reproductive technologies (ART) to circumvent infertility. Oocyte cryopreservation enables women to achieve genetically related offspring in the event that they desire to postpone their childbearing to an age after which a significant decline in fertility occurs or in circumstances in which their reproductive potential is compromised due to medical pathology. Available success rates and safety data following oocyte cryopreservation have been reassuring and is not considered experimental according to the American Society for Reproductive Medicine and the European Society for Human Reproduction and Embryology. This review article will focus on an evidence-based discussion relating to reproductive aging and oocyte cryopreservation.

Research paper thumbnail of Counseling patients on reproductive aging and elective fertility preservation—a survey of obstetricians and gynecologists’ experience, approach, and knowledge

Journal of Assisted Reproduction and Genetics

Research paper thumbnail of Comparison of perinatal outcomes following frozen embryo transfer cycles using autologous versus donor oocytes in women 40 to 43 years old: analysis of SART CORS data

Journal of Assisted Reproduction and Genetics

Research paper thumbnail of Elevated estradiol (E2) levels in artificial autologous frozen embryo transfer (FET) cycles negatively impact live birth (lb) and ongoing pregnancy (OP) rates

Research paper thumbnail of Does donor sperm affect birth weight (BW), preterm birth (PB), And miscarriage rates in fresh autologous in vitro fertilization (IVF) cycles? analysis of 46,061 cycles reported to SART

Research paper thumbnail of Elevated serum estradiol levels in artificial autologous frozen embryo transfer cycles negatively impact ongoing pregnancy and live birth rates

Journal of Assisted Reproduction and Genetics

Research paper thumbnail of Noninvasive detection of trophoblast protein signatures linked to early pregnancy loss using trophoblast retrieval and isolation from the cervix (TRIC)

Fertility and Sterility, 2015

To examine the expression pattern of biomarker proteins in extravillous trophoblast (EVT) cells o... more To examine the expression pattern of biomarker proteins in extravillous trophoblast (EVT) cells obtained noninvasively by trophoblast retrieval and isolation from the cervix (TRIC) in patients with early pregnancy loss compared with control patients with uncomplicated term delivery. Case-control study. Academic medical center. Women with either early pregnancy loss (EPL, n = 10) or an uncomplicated term delivery (N = 10). Endocervical specimens obtained from ongoing pregnancies at gestational ages of 5-10 weeks to generate an archive of EVT cells isolated by TRIC, with medical records examined to select specimens matched for gestational age at the time of endocervical sampling. Known serum biomarkers for adverse pregnancy outcome that are expressed by EVT cells were evaluated by semiquantitative immunocytochemistry, using antibodies against endoglin (ENG), FMS-like tyrosine kinase-1 (FLT-1), α-fetoprotein (AFP), pregnancy-associated plasma protein-A (PAPP-A), galectin-13 (LGALS13), ...

Research paper thumbnail of Altered Biomarkers in Trophoblast Cells Obtained Noninvasively Prior to Clinical Manifestation of Perinatal Disease

Scientific reports, Jan 23, 2016

A contributing factor to poor placental perfusion, leading to intrauterine growth restriction and... more A contributing factor to poor placental perfusion, leading to intrauterine growth restriction and preeclampsia, is the failure of invading extravillous trophoblast (EVT) cells to remodel the maternal uterine arteries during the first and second trimesters of pregnancy. Noninvasive assessment of EVT cells in ongoing pregnancies is possible beginning three weeks after conception, using trophoblast retrieval and isolation from the cervix (TRIC). Seven proteins were semi-quantified by immunofluorescence microscopy in EVT cells obtained between gestational weeks 6 and 20 from pregnancies with normal outcomes (N = 29) and those with intrauterine growth restriction or preeclampsia (N = 12). Significant differences were measured in expression of PAPPA, FLT1, ENG, AFP, PGF, and LGALS14, but not LGALS13 or the lineage marker KRT7. These findings provide for the first time direct evidence of pathology-associated protein dysregulation in EVT cells during early placentation. The TRIC platform pr...

Research paper thumbnail of Defragmentation of low grade day 3 embryos resulted in sustained reduction in fragmentation, but did not improve compaction or blastulation rates

Fertility and Sterility, 2010

In a prospective randomized fashion, this study evaluated embryo development in vitro after defra... more In a prospective randomized fashion, this study evaluated embryo development in vitro after defragmentation versus assisted hatching alone of low grade day 3 embryos. Although a sustained decrease in day 5 fragmentation was observed in the defragmented group versus the assisted hatching only group, no difference in compaction rates or blastula formation rates were appreciated. (Fertil Steril Ò 2010;94:2406-8. Ó2010 by American Society for Reproductive Medicine.

Research paper thumbnail of Successful Laparoscopically Assisted Transcervical Suction Evacuation of Interstitial Pregnancy following Failed Methotrexate Injection in a Community Hospital Setting

Case Reports in Obstetrics and Gynecology, 2014

We report on a case of a patient with an early diagnosed cornual ectopic pregnancy following fail... more We report on a case of a patient with an early diagnosed cornual ectopic pregnancy following failed methotrexate treatment. The patient was subsequently taken to the operating room for a laparoscopic guided transcervical suction curettage of the cornual ectopic. The surgery was successful and the patient was followed up until her urine pregnancy test was negative. We conclude that in properly selected patients, cornual ectopic pregnancy may be treated with transcervical suction curettage.

Research paper thumbnail of Noninvasive detection of trophoblast protein signatures linked to early pregnancy loss using trophoblast retrieval and isolation from the cervix (TRIC)

Fertility and Sterility, 2015

To examine the expression pattern of biomarker proteins in extravillous trophoblast (EVT) cells o... more To examine the expression pattern of biomarker proteins in extravillous trophoblast (EVT) cells obtained noninvasively by trophoblast retrieval and isolation from the cervix (TRIC) in patients with early pregnancy loss compared with control patients with uncomplicated term delivery. Case-control study. Academic medical center. Women with either early pregnancy loss (EPL, n = 10) or an uncomplicated term delivery (N = 10). Endocervical specimens obtained from ongoing pregnancies at gestational ages of 5-10 weeks to generate an archive of EVT cells isolated by TRIC, with medical records examined to select specimens matched for gestational age at the time of endocervical sampling. Known serum biomarkers for adverse pregnancy outcome that are expressed by EVT cells were evaluated by semiquantitative immunocytochemistry, using antibodies against endoglin (ENG), FMS-like tyrosine kinase-1 (FLT-1), α-fetoprotein (AFP), pregnancy-associated plasma protein-A (PAPP-A), galectin-13 (LGALS13), galectin-14 (LGALS14), and placental growth factor (PGF). The EVT purity was over 95% in all specimens, based on chorionic gonadotropin expression; however, the number of EVT cells obtained was significantly lower in women with EPL than the control group. There was a statistically significant elevation of AFP, ENG, and FLT-1, and statistically significant reduction of PAPP-A, LGALS14, and PGF in the EPL group compared with controls. In this pilot study, EVT cells isolated by TRIC early in gestation exhibited altered protein expression patterns before an EPL compared with uncomplicated term pregnancies.

Research paper thumbnail of Successful Laparoscopically Assisted Transcervical Suction Evacuation of Interstitial Pregnancy following Failed Methotrexate Injection in a Community Hospital Setting

Case reports in obstetrics and gynecology, 2014

We report on a case of a patient with an early diagnosed cornual ectopic pregnancy following fail... more We report on a case of a patient with an early diagnosed cornual ectopic pregnancy following failed methotrexate treatment. The patient was subsequently taken to the operating room for a laparoscopic guided transcervical suction curettage of the cornual ectopic. The surgery was successful and the patient was followed up until her urine pregnancy test was negative. We conclude that in properly selected patients, cornual ectopic pregnancy may be treated with transcervical suction curettage.

Research paper thumbnail of Cell signaling in trophoblast-uterine communication

The International Journal of Developmental Biology, 2014

Intricate and precise communication between the blastocyst and the uterus orchestrates embryo imp... more Intricate and precise communication between the blastocyst and the uterus orchestrates embryo implantation. However, many questions remain unanswered regarding the molecular complexities of implantation. On-time implantation requires a receptive uterus and a mature blastocyst with trophoblast cells capable of adhering to and invading the endometrium. Defects in uterine receptivity or embryo/uterine signaling can cause implantation failure or early pregnancy loss, whereas deficient trophoblast differentiation can generate placental abnormalities that produce adverse pregnancy outcomes. This review will discuss several examples of signaling pathways that regulate trophoblast and uterine development during this period. Leukemia inhibitory factor is involved in uterine priming for implantation. The epidermal growth factor signaling system contributes to trophoblast-uterine communication, as well as trophoblast adhesion and invasion. Indian hedgehog signaling synchronizes tissue compartments within the uterus, and WNT signaling mediates numerous interactions within the implantation site and developing placenta. The autocrine, paracrine and juxtacrine interactions mediated by these signaling pathways contribute significantly to the establishment of pregnancy, although there are many other known and yet to be discovered factors that synchronize the maternal and embryonic developmental programs.

Research paper thumbnail of Defragmentation of low grade day 3 embryos resulted in sustained reduction in fragmentation, but did not improve compaction or blastulation rates

Fertility and Sterility, 2010

In a prospective randomized fashion, this study evaluated embryo development in vitro after defra... more In a prospective randomized fashion, this study evaluated embryo development in vitro after defragmentation versus assisted hatching alone of low grade day 3 embryos. Although a sustained decrease in day 5 fragmentation was observed in the defragmented group versus the assisted hatching only group, no difference in compaction rates or blastula formation rates were appreciated. (Fertil Steril Ò 2010;94:2406-8. Ó2010 by American Society for Reproductive Medicine.

Research paper thumbnail of Trophoblast retrieval and isolation from the cervix (TRIC) for noninvasive prenatal screening at 5 to 20 weeks of gestation

Fertility and sterility

To use trophoblast cells accumulating in the endocervical canal at the beginning of pregnancy for... more To use trophoblast cells accumulating in the endocervical canal at the beginning of pregnancy for noninvasive prenatal testing. Prospective, double-blinded test for fetal gender. Academic medical center. Fifty-six women with singleton pregnancies at gestational age 5-20 weeks. Isolation of fetal cells from resident maternal cells in endocervical specimens using anti-human leukocyte antigen G coupled to magnetic nanoparticles; cell phenotyping immunofluorescently with a panel of trophoblast subtype-specific proteins; DNA integrity assessment with terminal dUTP nick-end labeling (TUNEL); and polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH) to detect sex chromosomes in individual cells. Trophoblast phenotype, TUNEL index, and percentage male cells. The women were given a routine Papanicolaou test; fetal genders were verified from medical records. Recovery after immunomagnetic isolation averaged 746 ± 59 cells across gestational age, with 99% expressing chori...

Research paper thumbnail of Fetal genome profiling at 5 weeks of gestation after noninvasive isolation of trophoblast cells from the endocervical canal

Science translational medicine, Jan 2, 2016

Single-gene mutations account for more than 6000 diseases, 10% of all pediatric hospital admissio... more Single-gene mutations account for more than 6000 diseases, 10% of all pediatric hospital admissions, and 20% of infant deaths. Down syndrome and other aneuploidies occur in more than 0.2% of births worldwide and are on the rise because of advanced reproductive age. Birth defects of genetic origin can be diagnosed in utero after invasive extraction of fetal tissues. Noninvasive testing with circulating cell-free fetal DNA is limited by a low fetal DNA fraction. Both modalities are unavailable until the end of the first trimester. We have isolated intact trophoblast cells from Papanicolaou smears collected noninvasively at 5 to 19 weeks of gestation for next-generation sequencing of fetal DNA. Consecutive matched maternal, placental, and fetal samples (n = 20) were profiled by multiplex targeted DNA sequencing of 59 short tandem repeat and 94 single-nucleotide variant sites across all 24 chromosomes. The data revealed fetal DNA fractions of 85 to 99.9%, with 100% correct fetal haploty...

Research paper thumbnail of In Vitro Fertilization vs Intracytoplasmic Sperm Injection for Non-Male Factor Preimplantation Genetic Testing-Aneuploidy Cycles: Are There Differences in Embryos Suitable for Transfer Pregnancy Outcomes? A Sart Cors Analysis

Research paper thumbnail of Elevated estradiol (E2) levels in artificial autologous frozen embryo transfer (FET) cycles negatively impact live birth (lb) and ongoing pregnancy (OP) rates

Research paper thumbnail of Dissociation of Pubertal Development Abnormality and Gonadal Dysfunction in Childhood Cancer Survivors

Journal of Adolescent and Young Adult Oncology

Purpose: To determine the relationship between pubertal development and postpubertal gonadal func... more Purpose: To determine the relationship between pubertal development and postpubertal gonadal function in childhood cancer survivors. Methods: Childhood cancer survivors (q10 years of age) who received follow-up care in a pediatric oncology group in an academic medical center during the period from January 1, 1985, to July 1, 2010 were included in this case series. Their pubertal development and gonadal function were evaluated. Results: The cohort consists of 39 males (age 10-21 years) and 35 females (age 10-29 years) with a variety of cancer diagnosis and treatments. The average age at diagnosis was *7.5 years. The average age at the time of the study was 16 and 16.7 years in males and females, respectively, representing a mean follow-up interval of *9 years. Despite the fact that 60% of survivors received cyclophosphamide equivalents and 16.2% received cranial radiation or brain tumor resection, the majority of survivors (68%) presented with both normal puberty and normal gonadal functions at the time of follow-up. In 27% of survivors, puberty development did not predict gonadal function in early adulthood: 20% of survivors had normal puberty, but abnormal gonadal function; 7% of survivors had abnormal puberty, but gonadal function remained normal as young adults. Conclusions: Most childhood cancer survivors had normal puberty and gonadal function despite a variety of cancer treatment modalities. However, normal puberty did not predict normal gonadal function later in life in many survivors. Therefore, close follow-up with gonadal function in adolescent and early adulthood years is essential.

Research paper thumbnail of Identification and characterization of RSIY-11, a novel seminal peptide derived from semenogelin-1, which acts as a neutral endopeptidase inhibitor modulating sperm motility

Journal of Assisted Reproduction and Genetics

Research paper thumbnail of Reproductive aging and elective fertility preservation

Journal of Ovarian Research

Reproductive aging is a natural process that occurs in all women, eventually leading to reproduct... more Reproductive aging is a natural process that occurs in all women, eventually leading to reproductive senescence and menopause. Over the past half century there has been a trend towards delayed motherhood. Postponing reproduction can increase the chance of a woman remaining involuntarily childless as well as an increase in pregnancy complications in those that do achieve pregnancy at advanced maternal age. Despite the well-documented decrease in fecundity that occurs as a woman ages, reproductive aged women frequently overestimate the age at which a significant decline in fertility occurs and overestimate the success of assisted reproductive technologies (ART) to circumvent infertility. Oocyte cryopreservation enables women to achieve genetically related offspring in the event that they desire to postpone their childbearing to an age after which a significant decline in fertility occurs or in circumstances in which their reproductive potential is compromised due to medical pathology. Available success rates and safety data following oocyte cryopreservation have been reassuring and is not considered experimental according to the American Society for Reproductive Medicine and the European Society for Human Reproduction and Embryology. This review article will focus on an evidence-based discussion relating to reproductive aging and oocyte cryopreservation.

Research paper thumbnail of Counseling patients on reproductive aging and elective fertility preservation—a survey of obstetricians and gynecologists’ experience, approach, and knowledge

Journal of Assisted Reproduction and Genetics

Research paper thumbnail of Comparison of perinatal outcomes following frozen embryo transfer cycles using autologous versus donor oocytes in women 40 to 43 years old: analysis of SART CORS data

Journal of Assisted Reproduction and Genetics

Research paper thumbnail of Elevated estradiol (E2) levels in artificial autologous frozen embryo transfer (FET) cycles negatively impact live birth (lb) and ongoing pregnancy (OP) rates

Research paper thumbnail of Does donor sperm affect birth weight (BW), preterm birth (PB), And miscarriage rates in fresh autologous in vitro fertilization (IVF) cycles? analysis of 46,061 cycles reported to SART

Research paper thumbnail of Elevated serum estradiol levels in artificial autologous frozen embryo transfer cycles negatively impact ongoing pregnancy and live birth rates

Journal of Assisted Reproduction and Genetics

Research paper thumbnail of Noninvasive detection of trophoblast protein signatures linked to early pregnancy loss using trophoblast retrieval and isolation from the cervix (TRIC)

Fertility and Sterility, 2015

To examine the expression pattern of biomarker proteins in extravillous trophoblast (EVT) cells o... more To examine the expression pattern of biomarker proteins in extravillous trophoblast (EVT) cells obtained noninvasively by trophoblast retrieval and isolation from the cervix (TRIC) in patients with early pregnancy loss compared with control patients with uncomplicated term delivery. Case-control study. Academic medical center. Women with either early pregnancy loss (EPL, n = 10) or an uncomplicated term delivery (N = 10). Endocervical specimens obtained from ongoing pregnancies at gestational ages of 5-10 weeks to generate an archive of EVT cells isolated by TRIC, with medical records examined to select specimens matched for gestational age at the time of endocervical sampling. Known serum biomarkers for adverse pregnancy outcome that are expressed by EVT cells were evaluated by semiquantitative immunocytochemistry, using antibodies against endoglin (ENG), FMS-like tyrosine kinase-1 (FLT-1), α-fetoprotein (AFP), pregnancy-associated plasma protein-A (PAPP-A), galectin-13 (LGALS13), ...

Research paper thumbnail of Altered Biomarkers in Trophoblast Cells Obtained Noninvasively Prior to Clinical Manifestation of Perinatal Disease

Scientific reports, Jan 23, 2016

A contributing factor to poor placental perfusion, leading to intrauterine growth restriction and... more A contributing factor to poor placental perfusion, leading to intrauterine growth restriction and preeclampsia, is the failure of invading extravillous trophoblast (EVT) cells to remodel the maternal uterine arteries during the first and second trimesters of pregnancy. Noninvasive assessment of EVT cells in ongoing pregnancies is possible beginning three weeks after conception, using trophoblast retrieval and isolation from the cervix (TRIC). Seven proteins were semi-quantified by immunofluorescence microscopy in EVT cells obtained between gestational weeks 6 and 20 from pregnancies with normal outcomes (N = 29) and those with intrauterine growth restriction or preeclampsia (N = 12). Significant differences were measured in expression of PAPPA, FLT1, ENG, AFP, PGF, and LGALS14, but not LGALS13 or the lineage marker KRT7. These findings provide for the first time direct evidence of pathology-associated protein dysregulation in EVT cells during early placentation. The TRIC platform pr...

Research paper thumbnail of Defragmentation of low grade day 3 embryos resulted in sustained reduction in fragmentation, but did not improve compaction or blastulation rates

Fertility and Sterility, 2010

In a prospective randomized fashion, this study evaluated embryo development in vitro after defra... more In a prospective randomized fashion, this study evaluated embryo development in vitro after defragmentation versus assisted hatching alone of low grade day 3 embryos. Although a sustained decrease in day 5 fragmentation was observed in the defragmented group versus the assisted hatching only group, no difference in compaction rates or blastula formation rates were appreciated. (Fertil Steril Ò 2010;94:2406-8. Ó2010 by American Society for Reproductive Medicine.

Research paper thumbnail of Successful Laparoscopically Assisted Transcervical Suction Evacuation of Interstitial Pregnancy following Failed Methotrexate Injection in a Community Hospital Setting

Case Reports in Obstetrics and Gynecology, 2014

We report on a case of a patient with an early diagnosed cornual ectopic pregnancy following fail... more We report on a case of a patient with an early diagnosed cornual ectopic pregnancy following failed methotrexate treatment. The patient was subsequently taken to the operating room for a laparoscopic guided transcervical suction curettage of the cornual ectopic. The surgery was successful and the patient was followed up until her urine pregnancy test was negative. We conclude that in properly selected patients, cornual ectopic pregnancy may be treated with transcervical suction curettage.

Research paper thumbnail of Noninvasive detection of trophoblast protein signatures linked to early pregnancy loss using trophoblast retrieval and isolation from the cervix (TRIC)

Fertility and Sterility, 2015

To examine the expression pattern of biomarker proteins in extravillous trophoblast (EVT) cells o... more To examine the expression pattern of biomarker proteins in extravillous trophoblast (EVT) cells obtained noninvasively by trophoblast retrieval and isolation from the cervix (TRIC) in patients with early pregnancy loss compared with control patients with uncomplicated term delivery. Case-control study. Academic medical center. Women with either early pregnancy loss (EPL, n = 10) or an uncomplicated term delivery (N = 10). Endocervical specimens obtained from ongoing pregnancies at gestational ages of 5-10 weeks to generate an archive of EVT cells isolated by TRIC, with medical records examined to select specimens matched for gestational age at the time of endocervical sampling. Known serum biomarkers for adverse pregnancy outcome that are expressed by EVT cells were evaluated by semiquantitative immunocytochemistry, using antibodies against endoglin (ENG), FMS-like tyrosine kinase-1 (FLT-1), α-fetoprotein (AFP), pregnancy-associated plasma protein-A (PAPP-A), galectin-13 (LGALS13), galectin-14 (LGALS14), and placental growth factor (PGF). The EVT purity was over 95% in all specimens, based on chorionic gonadotropin expression; however, the number of EVT cells obtained was significantly lower in women with EPL than the control group. There was a statistically significant elevation of AFP, ENG, and FLT-1, and statistically significant reduction of PAPP-A, LGALS14, and PGF in the EPL group compared with controls. In this pilot study, EVT cells isolated by TRIC early in gestation exhibited altered protein expression patterns before an EPL compared with uncomplicated term pregnancies.

Research paper thumbnail of Successful Laparoscopically Assisted Transcervical Suction Evacuation of Interstitial Pregnancy following Failed Methotrexate Injection in a Community Hospital Setting

Case reports in obstetrics and gynecology, 2014

We report on a case of a patient with an early diagnosed cornual ectopic pregnancy following fail... more We report on a case of a patient with an early diagnosed cornual ectopic pregnancy following failed methotrexate treatment. The patient was subsequently taken to the operating room for a laparoscopic guided transcervical suction curettage of the cornual ectopic. The surgery was successful and the patient was followed up until her urine pregnancy test was negative. We conclude that in properly selected patients, cornual ectopic pregnancy may be treated with transcervical suction curettage.

Research paper thumbnail of Cell signaling in trophoblast-uterine communication

The International Journal of Developmental Biology, 2014

Intricate and precise communication between the blastocyst and the uterus orchestrates embryo imp... more Intricate and precise communication between the blastocyst and the uterus orchestrates embryo implantation. However, many questions remain unanswered regarding the molecular complexities of implantation. On-time implantation requires a receptive uterus and a mature blastocyst with trophoblast cells capable of adhering to and invading the endometrium. Defects in uterine receptivity or embryo/uterine signaling can cause implantation failure or early pregnancy loss, whereas deficient trophoblast differentiation can generate placental abnormalities that produce adverse pregnancy outcomes. This review will discuss several examples of signaling pathways that regulate trophoblast and uterine development during this period. Leukemia inhibitory factor is involved in uterine priming for implantation. The epidermal growth factor signaling system contributes to trophoblast-uterine communication, as well as trophoblast adhesion and invasion. Indian hedgehog signaling synchronizes tissue compartments within the uterus, and WNT signaling mediates numerous interactions within the implantation site and developing placenta. The autocrine, paracrine and juxtacrine interactions mediated by these signaling pathways contribute significantly to the establishment of pregnancy, although there are many other known and yet to be discovered factors that synchronize the maternal and embryonic developmental programs.

Research paper thumbnail of Defragmentation of low grade day 3 embryos resulted in sustained reduction in fragmentation, but did not improve compaction or blastulation rates

Fertility and Sterility, 2010

In a prospective randomized fashion, this study evaluated embryo development in vitro after defra... more In a prospective randomized fashion, this study evaluated embryo development in vitro after defragmentation versus assisted hatching alone of low grade day 3 embryos. Although a sustained decrease in day 5 fragmentation was observed in the defragmented group versus the assisted hatching only group, no difference in compaction rates or blastula formation rates were appreciated. (Fertil Steril Ò 2010;94:2406-8. Ó2010 by American Society for Reproductive Medicine.

Research paper thumbnail of Trophoblast retrieval and isolation from the cervix (TRIC) for noninvasive prenatal screening at 5 to 20 weeks of gestation

Fertility and sterility

To use trophoblast cells accumulating in the endocervical canal at the beginning of pregnancy for... more To use trophoblast cells accumulating in the endocervical canal at the beginning of pregnancy for noninvasive prenatal testing. Prospective, double-blinded test for fetal gender. Academic medical center. Fifty-six women with singleton pregnancies at gestational age 5-20 weeks. Isolation of fetal cells from resident maternal cells in endocervical specimens using anti-human leukocyte antigen G coupled to magnetic nanoparticles; cell phenotyping immunofluorescently with a panel of trophoblast subtype-specific proteins; DNA integrity assessment with terminal dUTP nick-end labeling (TUNEL); and polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH) to detect sex chromosomes in individual cells. Trophoblast phenotype, TUNEL index, and percentage male cells. The women were given a routine Papanicolaou test; fetal genders were verified from medical records. Recovery after immunomagnetic isolation averaged 746 ± 59 cells across gestational age, with 99% expressing chori...

Research paper thumbnail of Fetal genome profiling at 5 weeks of gestation after noninvasive isolation of trophoblast cells from the endocervical canal

Science translational medicine, Jan 2, 2016

Single-gene mutations account for more than 6000 diseases, 10% of all pediatric hospital admissio... more Single-gene mutations account for more than 6000 diseases, 10% of all pediatric hospital admissions, and 20% of infant deaths. Down syndrome and other aneuploidies occur in more than 0.2% of births worldwide and are on the rise because of advanced reproductive age. Birth defects of genetic origin can be diagnosed in utero after invasive extraction of fetal tissues. Noninvasive testing with circulating cell-free fetal DNA is limited by a low fetal DNA fraction. Both modalities are unavailable until the end of the first trimester. We have isolated intact trophoblast cells from Papanicolaou smears collected noninvasively at 5 to 19 weeks of gestation for next-generation sequencing of fetal DNA. Consecutive matched maternal, placental, and fetal samples (n = 20) were profiled by multiplex targeted DNA sequencing of 59 short tandem repeat and 94 single-nucleotide variant sites across all 24 chromosomes. The data revealed fetal DNA fractions of 85 to 99.9%, with 100% correct fetal haploty...