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18 pages, 1622 KiB

Open AccessEditor’s ChoiceArticle

Identifying Predictive Bacterial Markers from Cervical Swab Microbiota on Pregnancy Outcome in Woman Undergoing Assisted Reproductive Technologies

by Annacandida Villani, Andrea Fontana, Stefano Barone, Silvia de Stefani, Mariangela Primiterra, Massimiliano Copetti, Concetta Panebianco, Cristiana Parri, Natale Sciannamè, Pasqua Anna Quitadamo, Alessandra Tiezzi, Liliana Santana, Annamaria Maglione, Federica D’Amato, Francesco Perri, Simone Palini and Valerio Pazienza

J. Clin. Med. 2022, 11(3), 680; https://doi.org/10.3390/jcm11030680 - 28 Jan 2022

Cited by 10 | Viewed by 2259

Abstract

Background and aims: Failure of the embryo to implant causes about three-fourths of lost pregnancies. Female genital tract microbiota has been associated to Assisted Reproductive Technologies (ART) outcomes. The objective of this study was to analyze the microbiota of human cervical swab and [...] Read more.

Background and aims: Failure of the embryo to implant causes about three-fourths of lost pregnancies. Female genital tract microbiota has been associated to Assisted Reproductive Technologies (ART) outcomes. The objective of this study was to analyze the microbiota of human cervical swab and to correlate these findings with the ART outcomes. Materials and Methods: In this study, 88 cervical swabs were collected from women undergoing ART cycles, with various causes of infertility, at the beginning of the ART protocols. After microbial DNA extraction, V3–V4 variable regions of the 16S rRNA gene were amplified and sequenced on the Illumina MiSeq platform. PEnalized LOgistic Regression Analysis (PELORA) was performed to identify clusters of bacterial populations with differential abundances between patients with unfavorable and favorable pregnancy outcome groups, respectively. Results: We identified a core of microorganisms at lower taxonomic levels that were predictive of women’s pregnancy outcomes. Statistically significant differences were identified at species levels with Lactobacillus salivarius, Lactobacillus rhamnosus among others. Moreover the abundance of Lactobacillus crispatus and iners, respectively increased and decreased in favorable group as compared to unfavorable group, resulted within the core of microorganisms associated to positive ART outcome. Although the predominance of lactobacilli is generally considered to be advantageous for ART outcome, we found that also the presence of Bifidobacterium (together with the other lactobacilli) was more abundant in the favorable group. Discussion: Cervix is colonized by microorganisms which can play a role in ART outcomes as seen by an overall decrease in embryo attachment rates and pregnancy rates in both fertile and infertile women. If confirmed in a larger cohort, the abundance of these bacteria can be useful not only as a marker of unfavorable pregnancy outcome but also they may open the way to new interventional strategies based on genital tract microbiota manipulation in order to increase the pregnancy rates in woman undergoing assisted reproductive technologies. Full article

(This article belongs to the Special Issue Assisted Reproductive Technology and Pregnancy Outcomes)

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20 pages, 10029 KiB

Open AccessArticle

Risk Assessment of the Increased Occurrence of Congenital Cardiac and Non-Cardiac Defects in Fetuses with a Normal Karyotype after Assisted Fertilization in Comparison to Natural Fertilization Based on Ultrasound Diagnostics

by Dawid Serafin, Beniamin Oskar Grabarek, Dariusz Boroń, Andrzej Madej and Bartosz Czuba

J. Clin. Med. 2021, 10(23), 5630; https://doi.org/10.3390/jcm10235630 - 29 Nov 2021

Cited by 4 | Viewed by 2089

Abstract

The goal of the study was to assess changes in parameters based on ultrasound examinations—these were Crown Rump Length (CRL), Nuchal Translucency (NT), Fetal Heart Rate (FHR), and Pulsatility Index for Ductus Venosus (DV-PI)—in the first trimester of pregnancy in women in which [...] Read more.

The goal of the study was to assess changes in parameters based on ultrasound examinations—these were Crown Rump Length (CRL), Nuchal Translucency (NT), Fetal Heart Rate (FHR), and Pulsatility Index for Ductus Venosus (DV-PI)—in the first trimester of pregnancy in women in which there was a natural initiation of the pregnancy due to spontaneous ovulation, women in which the pregnancy was initiated as a result of stimulated ovulation, as well as in the group in which pregnancy was achieved through the use of In-Vitro Fertilization (IVF)-assisted reproduction. A total of 1581 women became pregnant without the use of assisted reproduction methods. Out of 283 pregnancies, in 178 patients, induced ovulation was utilized. Next, 137 women had sexual intercourse and became pregnant; 41 of them became pregnant through Intrauterine Insemination (IUI) as a result of Artificial Insemination by Husband (AIH), and 13 became pregnant after Artificial Insemination by Donor (AID). The third group consisted of 105 women subjected to Controlled Ovarian Hyperstimulation (COH). In this group of pregnant women, 53 pregnancies were resultant of Intracytoplasmic Sperm Injection (ICSI), and 52 pregnancies were the result of Intracytoplasmic Morphologically selected Sperm Injection (IMSI). The obtained results did not indicate that the chosen method of fertilization or the chosen ovulation method had a statistically significant effect on the development risk of congenital heart or non-heart defects in the fetus. Full article

(This article belongs to the Special Issue Assisted Reproductive Technology and Pregnancy Outcomes)

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14 pages, 1265 KiB

Open AccessArticle

National Survey Highlights the Urgent Need for Standardisation of Embryo Transfer Techniques in the UK

by Lewis Nancarrow, Nicola Tempest, Andrew J. Drakeley, Roy Homburg, Richard Russell and Dharani K. Hapangama

J. Clin. Med. 2021, 10(13), 2839; https://doi.org/10.3390/jcm10132839 - 27 Jun 2021

Cited by 4 | Viewed by 2091

Abstract

Embryo transfer (ET) is one of the vital steps in the in vitro fertilisation (IVF) process, yet there is wide variation in ET technique throughout the UK, without a nationally approved standardised approach. The aim of this study was to gain contemporaneous information [...] Read more.

Embryo transfer (ET) is one of the vital steps in the in vitro fertilisation (IVF) process, yet there is wide variation in ET technique throughout the UK, without a nationally approved standardised approach. The aim of this study was to gain contemporaneous information regarding the current clinical ET practice in the UK. Method: A 38-question electronic survey was distributed to the 79 UK Human Fertilisation and Embryology Authority (HFEA) registered clinics performing ETs. Results: In total, 59% (47/79) of units responded, 83% (39/47) performing ultrasound-guided transfers, with 42% (20/47) of units using a tenaculum; 22% (10/45) would proceed with transfer regardless of fluid in the endometrial cavity. In 91% (43/47) of units, embryos were deposited in the upper/middle portion of the uterine cavity, but interpretation of this area ranged from 0.5 to >2 cm from the fundus, with 68% (32/47) allowing patients to mobilise immediately after transfer. In 60% (27/45) of clinics, success rates were based on clinical pregnancy rates (CPR). Conclusion: Within the UK there is a wide range of variability in ET techniques, with >70% of discordance in survey-responses between clinics. Whilst there are areas of good practice, some disadvantageous techniques continue to persist. This survey emphasises the importance of developing a standardised, evidence-based approach to improve ET success rates. Full article

(This article belongs to the Special Issue Assisted Reproductive Technology and Pregnancy Outcomes)

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15 pages, 369 KiB

Open AccessArticle

Disparities in ART Live Birth and Cumulative Live Birth Outcomes for Hispanic and Asian Women Compared to White Non-Hispanic Women

by Alexander M. Kotlyar, Burcin Simsek and David B. Seifer

J. Clin. Med. 2021, 10(12), 2615; https://doi.org/10.3390/jcm10122615 - 14 Jun 2021

Cited by 12 | Viewed by 1859

Abstract

BACKGROUND: Conflicting disparities have been seen in assisted reproductive technology (ART) outcomes for Hispanic and Asian women compared to white, non-Hispanic (WNH) women. We, therefore, sought to clarify these disparities and calculated cumulative live birth rates (CLBR) for these racial or ethnic groups [...] Read more.

BACKGROUND: Conflicting disparities have been seen in assisted reproductive technology (ART) outcomes for Hispanic and Asian women compared to white, non-Hispanic (WNH) women. We, therefore, sought to clarify these disparities and calculated cumulative live birth rates (CLBR) for these racial or ethnic groups using the SARTCORS database. METHODS: We performed an analysis of the 2014–2016 SARTCORS database for member clinics doing at least 50 cycles of ART each year. RESULTS: In comparison to cycles in WNH women, cycles in Hispanic and Asian patients were in older (p < 0.001), more nulliparous women, that were less likely to have a history of endometriosis compared WNH women regardless of prior ART status. ART cycles in Hispanic and Asian women, exhibited lower rates of live birth (LB) per cycle start (p < 0.001) compared to cycles in WNH women. Multivariate logistic regression demonstrated that cycles from Hispanic and Asian women were less likely to have a LB and CLBR than white women (OR 0.86; p = 0.004, OR 0.69; p < 0.001, respectively) independent of age, parity, BMI, etiology of infertility, use of ICSI or number of embryos transferred. CONCLUSIONS: Race or ethnicity continues to be an independent prognostic factor for LB and CLBR for ART. Additional analysis of trends among Hispanic and Asian women is warranted to enable addressing disparities in outcomes in ART treatment. Full article

(This article belongs to the Special Issue Assisted Reproductive Technology and Pregnancy Outcomes)

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12 pages, 258 KiB

Open AccessArticle

Influence of Placental Abnormalities and Pregnancy-Induced Hypertension in Prematurity Associated with Various Assisted Reproductive Technology Techniques

by Judy E. Stern, Chia-ling Liu, Sunah S. Hwang, Dmitry Dukhovny, Leslie V. Farland, Hafsatou Diop, Charles C. Coddington and Howard Cabral

J. Clin. Med. 2021, 10(8), 1681; https://doi.org/10.3390/jcm10081681 - 14 Apr 2021

Cited by 8 | Viewed by 1786

Abstract

Objective. Assisted reproductive technology (ART)-treated women exhibit increased risk of premature delivery compared to fertile women. We evaluated whether ART treatment modalities increase prematurity and whether placental abnormalities and pregnancy-induced hypertensive (PIH) disorders mediate these risks. Method(s): This retrospective study of ART-treated and [...] Read more.

Objective. Assisted reproductive technology (ART)-treated women exhibit increased risk of premature delivery compared to fertile women. We evaluated whether ART treatment modalities increase prematurity and whether placental abnormalities and pregnancy-induced hypertensive (PIH) disorders mediate these risks. Method(s): This retrospective study of ART-treated and fertile deliveries (2004–2017) used an ART-cycle database linked to Massachusetts birth certificates and hospital discharges. Outcomes of late preterm birth (LPTB: 34–36 weeks gestation) and early preterm birth (EPTB: <34 weeks gestation) were compared with term deliveries (≥37 weeks gestation) in ART-treated (linked to the ART database) and fertile (no indicators of infertility or ART) deliveries. ART treatments with autologous oocyte, donor oocyte, fresh or frozen embryo transfer (FET), intracytoplasmic sperm injection (ICSI) and no-ICSI were separately compared to the fertile group. Adjusted odds ratios (AOR) were calculated with multivariable logistic regression: placental abnormalities or PIH were quantified in the pathway as mediators. Results: There were 218,320 deliveries: 204,438 fertile and 13,882 ART-treated. All treatment types increased prematurity (AOR 1.31–1.58, LPTB; AOR 1.34–1.48, EPTB). Placental abnormalities mediated in approximately 22% and 38% of the association with LPTB and EPTB, respectively. PIH mediated 25% and 33% of the association with LPTB and EPTB in FET and donor oocyte cycles, more than other treatments (<10% LPTB and <13% EPTB). Conclusions: ART-treatment and all ART modalities increased LPTB and EPTB when compared with fertile deliveries. Placental abnormalities modestly mediated associations approximately equally, while PIH was a stronger mediator in FET and donor oocyte cycles. Reasons for differences require exploration. Full article

(This article belongs to the Special Issue Assisted Reproductive Technology and Pregnancy Outcomes)

14 pages, 1844 KiB

Open AccessArticle

Negative Impact of Elevated DNA Fragmentation and Human Papillomavirus (HPV) Presence in Sperm on the Outcome of Intra-Uterine Insemination (IUI)

by Christophe Depuydt, Gilbert Donders, Ludo Verstraete, Johan Beert, Geert Salembier, Eugene Bosmans, Nathalie Dhont, Carmen Kerkhofs and Willem Ombelet

J. Clin. Med. 2021, 10(4), 717; https://doi.org/10.3390/jcm10040717 - 11 Feb 2021

Cited by 12 | Viewed by 2466

Abstract

We wanted to determine the sperm DNA fragmentation index (DFI) cutoff for clinical pregnancies in women receiving intra-uterine insemination (IUI) with this sperm and to assess the contribution of Human Papillomavirus (HPV) infection on sperm DNA damage and its impact on clinical pregnancies. [...] Read more.

We wanted to determine the sperm DNA fragmentation index (DFI) cutoff for clinical pregnancies in women receiving intra-uterine insemination (IUI) with this sperm and to assess the contribution of Human Papillomavirus (HPV) infection on sperm DNA damage and its impact on clinical pregnancies. Prospective non-interventional multi-center study with 161 infertile couples going through 209 cycles of IUI in hospital fertility centers in Flanders, Belgium. Measurement of DFI and HPV DNA with type specific quantitative PCRs (HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68) in sperm before its use in IUI. Clinical pregnancy (CP) rate was used as the outcome to analyze the impact on fertility outcome and to calculated the clinical cutoff value for DFI. A DFI criterion value of 26% was obtained by receiver operating characteristic (ROC) curve analysis. Couples with a male DFI > 26% had significantly less CPs than couples with DFI below 26% (OR 0.0326; 95% CI 0.0019 to 0.5400; p = 0.017). In sperm, HPV prevalence was 14.8%/IUI cycle. Sperm samples containing HPV had a significantly higher DFI compared to HPV negative sperm samples (29.8% vs. 20.9%; p = 0.011). When HPV-virions were present in sperm, no clinical pregnancies were observed. More than 1 in 5 of samples with normal semen parameters (17/78; 21.8%) had an elevated DFI or was HPV positive. Sperm DFI is a robust predictor of clinical pregnancies in women receiving IUI with this sperm. When DFI exceeds 26%, clinical pregnancies are less likely and in vitro fertilization techniques should be considered. Full article

(This article belongs to the Special Issue Assisted Reproductive Technology and Pregnancy Outcomes)

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Review

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11 pages, 240 KiB

Open AccessReview

The Impact of Intracytoplasmic Sperm Injection in Non-Male Factor Infertility—A Critical Review

by Tanya L. Glenn, Alex M. Kotlyar and David B. Seifer

J. Clin. Med. 2021, 10(12), 2616; https://doi.org/10.3390/jcm10122616 - 14 Jun 2021

Cited by 15 | Viewed by 2796

Abstract

Intracytoplasmic sperm injection (ICSI) was originally designed to overcome barriers due to male factor infertility. However, a surveillance study found that ICSI use in non-male factor infertility increased from 15.4% to 66.9% between 1996 and 2012. Numerous studies have investigated fertilization rate, total [...] Read more.

Intracytoplasmic sperm injection (ICSI) was originally designed to overcome barriers due to male factor infertility. However, a surveillance study found that ICSI use in non-male factor infertility increased from 15.4% to 66.9% between 1996 and 2012. Numerous studies have investigated fertilization rate, total fertilization failure, and live birth rate per cycle (LBR), comparing the use of ICSI versus conventional in vitro fertilization (IVF) for non-male factor infertility. The overwhelming conclusion shows no increase in fertilization rate or LBR per cycle with the use of ICSI for non-male factor infertility. The overuse of ICSI is likely related to the desire to avoid a higher rate of total fertilization failure in IVF. However, data supporting the benefit of using ICSI for non-male factor infertility is lacking, and 33 couples would need to be treated with ICSI unnecessarily to avoid one case of total fertilization failure. Such practice increases the cost to the patient, increases the burden on embryologist’s time, and is a misapplication of resources. Additionally, there remains conflicting data regarding the safety of offspring conceived by ICSI and potential damage to the oocyte. Thus, the use of ICSI should be limited to those with male factor infertility or a history of total fertilization factor infertility due to uncertainties of potential adverse impact and lack of proven benefit in non-male factor infertility. Full article

(This article belongs to the Special Issue Assisted Reproductive Technology and Pregnancy Outcomes)

12 pages, 259 KiB

Open AccessReview

Pregnancy and Neonatal Outcomes after Transfer of Mosaic Embryos: A Review

by Sina Abhari and Jennifer F. Kawwass

J. Clin. Med. 2021, 10(7), 1369; https://doi.org/10.3390/jcm10071369 - 27 Mar 2021

Cited by 27 | Viewed by 3931

Abstract

Preimplantation genetic testing for aneuploidy (PGT-A) seeks to identify embryos with a normal chromosome complement during in vitro fertilization (IVF). Transfer of one euploid embryo at a time maximizes the chance of implantation while minimizing the risk of multiple pregnancy. The emergence of [...] Read more.

Preimplantation genetic testing for aneuploidy (PGT-A) seeks to identify embryos with a normal chromosome complement during in vitro fertilization (IVF). Transfer of one euploid embryo at a time maximizes the chance of implantation while minimizing the risk of multiple pregnancy. The emergence of new technologies including next generation sequencing (NGS) has led to increased diagnosis of embryonic mosaicism, suggesting the presence of karyotypically distinct cells within a single trophectoderm (TE). Clinical implications of embryonic mosaicism are important in both naturally conceived and IVF pregnancies. Although information regarding outcomes after mosaic embryo transfer (MET) is limited, more than 100 live births have now been documented with rather reassuring outcomes with no abnormal phenotype. Here, we aim to provide a summary of recent data regarding clinical and neonatal outcomes after transfer of mosaic embryos in IVF/PGT-A cycles. Full article

(This article belongs to the Special Issue Assisted Reproductive Technology and Pregnancy Outcomes)

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