Does endometriosis increase obstetric and neonatal complications, and does assisted reproductive technology (ART) cause additional risk of maternal or fetal morbidity?
A nationwide cohort study ...(2013–2018) comparing maternal and perinatal morbidities in three groups of single pregnancies: spontaneous pregnancies without endometriosis; spontaneous pregnancies with endometriosis; and ART pregnancies in women with endometriosis.
Mean maternal ages were 30.0 (SD = 5.3), 31.7 (SD = 4.8) and 33.1 years (SD = 4.0), for spontaneous conceptions, spontaneous conceptions with endometriosis and ART pregnancies with endometriosis groups, respectively (P < 0.0001). Comparison of spontaneous conceptions with endometriosis and spontaneous conceptions: endometriosis independently increased the risk of venous thrombosis (adjusted OR aOR 1.51, P < 0.001), pre-eclampsia (aOR 1.29, P < 0.001), placenta previa (aOR 2.62, P < 0.001), placental abruption (aOR 1.54, P < 0.001), premature birth (aOR 1.37, P < 0.001), small for gestational age (aOR 1.05, P < 0.001) and malformations (aOR 1.06, P = 0.049). Comparison of ART pregnancies with endometriosis and spontaneous conceptions with endometriosis: ART increased the risk of placenta previa (aOR 2.43, 95% CI 2.10 to 2.82, P < 0.001), premature birth (aOR 1.42, 95% CI 1.29 to 1.55, P < 0.001) and small for gestational age (aOR 1.18, 95% CI 1.10 to 1.27, P < 0.001), independently from the effect of endometriosis. Risk of pre-eclampsia, placental abruption or congenital malformations was not increased with ART.
Endometriosis is an independent risk factor for mother and child morbidities. Maternal morbidity and perinatal morbidity were significantly increased by ART in addition to endometriosis; however, some perinatal and maternal morbidity risks were increasingly linked to pathologies related to infertility.
To the best of our knowledge, no study has exhaustively evaluated the association between maternal morbidities and Coronavirus Disease 2019 (COVID-19) during the first wave of the pandemic in ...pregnant women. We investigated, in natural conceptions and assisted reproductive technique (ART) pregnancies, whether maternal morbidities were more frequent in pregnant women with COVID-19 diagnosis compared to pregnant women without COVID-19 diagnosis during the first wave of the COVID-19 pandemic. We conducted a retrospective analysis of prospectively collected data in a national cohort of all hospitalizations for births greater than or equal to22 weeks of gestation in France from January to June 2020 using the French national hospitalization database (PMSI). Pregnant women with COVID-19 were identified if they had been recorded in the database using the ICD-10 (International Classification of Disease) code for presence of a hospitalization for COVID-19. A total of 244,645 births were included, of which 874 (0.36%) in the COVID-19 group. Maternal morbidities and adverse obstetrical outcomes among those with or without COVID-19 were analyzed with a multivariable logistic regression model adjusted on patient characteristics. Among pregnant women, older age (31.1 (±5.9) years old versus 30.5 (±5.4) years old, respectively, p < 0.001), obesity (0.7% versus 0.3%, respectively, p < 0.001), multiple pregnancy (0.7% versus 0.4%, respectively, p < 0.001), and history of hypertension (0.9% versus 0.3%, respectively, p < 0.001) were more frequent with COVID-19 diagnosis. Active smoking (0.2% versus 0.4%, respectively, p < 0.001) and primiparity (0.3% versus 0.4%, respectively, p < 0.03) were less frequent with COVID-19 diagnosis. Frequency of ART conception was not different between those with and without COVID-19 diagnosis (p = 0.28). We observed an increased frequency of pregnant women with maternal morbidities and diagnosis of COVID-19 compared to pregnant women without COVID-19. It appears essential to be aware of this, notably in populations at known risk of developing a more severe form of infection or obstetrical morbidities and in order for obstetrical units to better inform pregnant women and provide the best care. Although causality cannot be determined from these associations, these results may be in line with recent recommendations in favor of vaccination for pregnant women.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND: Although intrauterine insemination (IUI) is one of the most common assisted reproductive technology methods in the world, the relative influence of various semen characteristics on the ...likelihood of a successful outcome is controversial. The aim of our study was to assess the results of IUI as a function of both the number of motile spermatozoa inseminated (NMSI) and the percentage of morphologically normal spermatozoa after preparation. METHODS: This was a retrospective study of 889 couples who underwent 2564 IUI cycles of ovarian stimulation with HMG or recombinant FSH in our centre between January 1991 and December 2000. RESULTS: A total of 331 clinical pregnancies were obtained, for a pregnancy rate/cycle of 12.91%. When the NMSI was <1 × 106, the pregnancy rate/cycle was significantly lower (3.13%) than in any of the subgroups with NMSI ≥2 × 106. Sperm morphology, assessed before or after preparation, was not in itself a significant factor that affected the likelihood of IUI success. Nonetheless, when the post-migration rate of normal sperm was <30%, the pregnancy rate/cycle was 5.43% when NMSI was <5 × 106 and 18.42% when NMSI was ≥5 × 106 (P=0.008). Pregnancy rates did not differ significantly according to NMSI when the percentage of normal sperm after preparation was ≥30%, or according to percentage of normal sperm when the NMSI was ≥5 × 106. CONCLUSIONS: Our results show that a minimum of 5 × 106 motile spermatozoa should be inseminated when the normal morphology of the sperm after preparation is <30%; the quantity compensates at least in part for the defective quality. If this threshold of NMSI cannot be obtained, IVF should be recommended.
To the best of our knowledge, no study has exhaustively evaluated the association between maternal morbidities and Coronavirus Disease 2019 (COVID-19) during the first wave of the pandemic in ...pregnant women. We investigated, in natural conceptions and assisted reproductive technique (ART) pregnancies, whether maternal morbidities were more frequent in pregnant women with COVID-19 diagnosis compared to pregnant women without COVID-19 diagnosis during the first wave of the COVID-19 pandemic.
We conducted a retrospective analysis of prospectively collected data in a national cohort of all hospitalizations for births ≥22 weeks of gestation in France from January to June 2020 using the French national hospitalization database (PMSI). Pregnant women with COVID-19 were identified if they had been recorded in the database using the ICD-10 (International Classification of Disease) code for presence of a hospitalization for COVID-19. A total of 244,645 births were included, of which 874 (0.36%) in the COVID-19 group. Maternal morbidities and adverse obstetrical outcomes among those with or without COVID-19 were analyzed with a multivariable logistic regression model adjusted on patient characteristics. Among pregnant women, older age (31.1 (±5.9) years old versus 30.5 (±5.4) years old, respectively, p < 0.001), obesity (0.7% versus 0.3%, respectively, p < 0.001), multiple pregnancy (0.7% versus 0.4%, respectively, p < 0.001), and history of hypertension (0.9% versus 0.3%, respectively, p < 0.001) were more frequent with COVID-19 diagnosis. Active smoking (0.2% versus 0.4%, respectively, p < 0.001) and primiparity (0.3% versus 0.4%, respectively, p < 0.03) were less frequent with COVID-19 diagnosis. Frequency of ART conception was not different between those with and without COVID-19 diagnosis (p = 0.28). When compared to the non-COVID-19 group, women in the COVID-19 group had a higher frequency of admission to ICU (5.9% versus 0.1%, p < 0.001), mortality (0.2% versus 0.005%, p < 0.001), preeclampsia/eclampsia (4.8% versus 2.2%, p < 0.001), gestational hypertension (2.3% versus 1.3%, p < 0.03), postpartum hemorrhage (10.0% versus 5.7%, p < 0.001), preterm birth at <37 weeks of gestation (16.7% versus 7.1%, p < 0.001), <32 weeks of gestation (2.2% versus 0.8%, p < 0.001), <28 weeks of gestation (2.4% versus 0.8%, p < 0.001), induced preterm birth (5.4% versus 1.4%, p < 0.001), spontaneous preterm birth (11.3% versus 5.7%, p < 0.001), fetal distress (33.0% versus 26.0%, p < 0.001), and cesarean section (33.0% versus 20.2%, p < 0.001). Rates of pregnancy terminations ≥22 weeks of gestation, stillbirths, gestational diabetes, placenta praevia, and placenta abruption were not significantly different between the COVID-19 and non-COVID-19 groups. The number of venous thromboembolic events was too low to perform statistical analysis. A limitation of this study relies in the possibility that asymptomatic infected women were not systematically detected.
We observed an increased frequency of pregnant women with maternal morbidities and diagnosis of COVID-19 compared to pregnant women without COVID-19. It appears essential to be aware of this, notably in populations at known risk of developing a more severe form of infection or obstetrical morbidities and in order for obstetrical units to better inform pregnant women and provide the best care. Although causality cannot be determined from these associations, these results may be in line with recent recommendations in favor of vaccination for pregnant women.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND: A testis biopsy was performed for four non-mosaic 47,XXY azoospermic patients. Spermatozoa were found in three cases and frozen before ICSI. We analysed the various cells found in the ...four samples by multicolour fluorescence in-situ hybridization (FISH), to evaluate the meiosis and spermatogenesis possibilities of the 47,XXY and 46,XY testis cell lines, and to estimate aneuploidy rate in the resulting spermatids and spermatozoa. METHODS AND RESULTS: Testis diploid cells (either somatic or premeiotic), meiotic, and post-meiotic haploid germ cells were hybridized with probes for chromosomes X, Y and 18. The only patient with no spermatozoa had a homogeneous diploid XXY constitution in the testis; the three other patients presented two cell populations (46,XY and 47,XXY) among their diploid testis cells. All the observed pachytene figures were XY; no XXY pachytene figure was found. The aneuploidy rate among post-meiotic cells for chromosomes X,Y and 18 was 6.75% (5/74). This rate was 1.5% (2/133) for control. Three couples underwent ICSI; four attempts were made, one healthy baby was born. CONCLUSION: FISH results suggest that only 46,XY cells can undergo meiosis.
To provide practice guidelines about fertility preservation (FP) in oncology.
We selected 400 articles after a PubMed review of the literature (1987–2019).
Any child, adolescent and adult of ...reproductive age should be informed about the risk of treatment gonadotoxicity.
In women, systematically proposed FP counselling between 15 and 38 years of age in case of treatment including bifunctional alkylating agents, above 6 g/m2 cyclophosphamide equivalent dose (CED), and for radiation doses on the ovaries ≥3 Gy.
For postmenarchal patients, oocyte cryopreservation after ovarian stimulation is the first-line FP technique.
Ovarian tissue cryopreservation should be discussed as a first-line approach in case of treatment with a high gonadotoxic risk, when chemotherapy has already started and in urgent cases.
Ovarian transposition is to be discussed prior to pelvic radiotherapy involving a high risk of premature ovarian failure.
For prepubertal girls, ovarian tissue cryopreservation should be proposed in the case of treatment with a high gonadotoxic risk.
In pubertal males, sperm cryopreservation must be systematically offered to any male who is to undergo cancer treatment, regardless of toxicity. Testicular tissue cryopreservation must be proposed in males unable to cryopreserve sperm who are to undergo a treatment with intermediate or severe risk of gonadotoxicity.
In prepubertal boys, testicular tissue preservation is:
- recommended for chemotherapy with a CED ≥7500 mg/m2 or radiotherapy ≥3 Gy on both testicles.
- proposed for chemotherapy with a CED ≥5.000 mg/m2 or radiotherapy ≥2 Gy.
If several possible strategies, the ultimate choice is made by the patient.
•Gonadal tissue preservation is indicated in children with a high risk of infertility.•Semen cryopreservation should be proposed to all cancer men and adolescents.•Fertility preservation is indicated in all women with a high risk of infertility.•Oocyte cryopreservation is the first-line technique in postmenarchal women.•Ovarian tissue preservation is indicated in case of very high risk of infertility.
Abstract
STUDY QUESTION
Do IVF, IUI or female infertility (i.e. endometriosis, polycystic ovary syndrome PCOS and primary ovarian insufficiency POI) lead to an increased risk of congenital anomalies ...in singletons?
SUMMARY ANSWER
After multivariable adjustments, the increased risks of congenital defects associated with IUI were no longer significant, but the underlying maternal infertility presented a potential emental risk, in addition to the risk associated with IVF.
WHAT IS KNOWN ALREADY
Most epidemiological studies suggest that singletons born from ART have a higher risk of birth defects, specifically musculoskeletal, cardiovascular and urogenital disorders. However, most of these studies were established on data obtained at birth or in the neonatal period and from relatively small populations or several registries. Moreover, to our knowledge, female infertility, which is a potential confounder, has never been included in the risk assessment.
STUDY DESIGN, SIZE, DURATION
Using data from the French National Health System database, we conducted a comparative analysis of all singleton births (deliveries ≥22 weeks of gestation and/or >500 g of birthweight) in France over a 5-year period (2013–2017) resulting from fresh embryo or frozen embryo transfer (fresh-ET or FET from IVF/ICSI cycles), IUI and natural conception (NC). Data were available for this cohort of children at least up to early childhood (2.5 years old).
PARTICIPANTS/MATERIALS, SETTING, METHODS
A total of 3 501 495 singleton births were included (3 417 089 from NC, 20 218 from IUI, 45 303 from fresh-ET and 18 885 from FET). Data were extracted from national health databases and used to identify major birth defects. Malformations were classified according to the 10th revision of the International Classification of Disease. To analyse the effect of mode of conception, multivariable analyses were performed with multiple logistic regression models adjusted for maternal age, primiparity, obesity, smoking, history of high blood pressure or diabetes and female infertility.
MAIN RESULTS AND THE ROLE OF CHANCE
In our cohort of children, the overall prevalence of congenital malformations was 3.78% after NC, 4.53% after fresh-ET, 4.39% after FET and 3.91% after IUI (132 646 children with major malformations). Compared with infants conceived naturally, children born after fresh-ET and after FET had a significantly higher prevalence of malformations, with an adjusted odds ratio (aOR) of 1.15 95% CI 1.10–1.20, P < 0.0001 and aOR of 1.13 95% CI 1.05–1.21, P = 0.001, respectively. Among the 15 relevant subgroups of malformations studied, we observed a significantly increased risk of eight malformations in the fresh-ET group compared with the NC group (i.e. musculoskeletal, cardiac, urinary, digestive, neurological, cleft lip and/or palate and respiratory). In the FET group, this increased risk was observed for digestive and facial malformations. The overall risk of congenital malformations, and the risk by subtype, was similar in the IUI group and the NC group (overall risk: aOR of 1.01 95% CI 0.94–1.08, P = 0.81). In addition, there was an overall independent increase in the risk of congenital defects when the mothers were diagnosed with endometriosis (1.16 aOR 95% CI 1.10–1.22, P < 0.0001), PCOS (1.20 aOR 95% CI 1.08–1.34, P = 0.001) or POI (1.52 aOR 95% CI 1.23–1.88, P = 0.0001). Chromosomal, cardiac and neurological anomalies were more common in the three maternal infertility groups.
LIMITATIONS, REASONS FOR CAUTION
Male infertility, the in vitro fertilization method (i.e. in vitro fertilization without or with sperm injection: conventional IVF vs ICSI) and embryo stage at transfer could not be taken into account. Furthermore, residual confounding cannot be excluded as well as uncertainties regarding the diagnostic criteria used for the three female infertilities. Findings for specific malformations should be interpreted with caution because the number of cases was small in some sub-groups (potentially due to the Type I error or multiple testing).
WIDER IMPLICATIONS OF THE FINDINGS
In this large study, after multivariable maternal adjustments, a moderately increased risk of defects subsisted after IVF, while those associated with IUI were no longer significant. In addition, our results showed that underlying maternal infertility could contribute to the increased risk of defects associated with IVF. These novel findings highlight the importance of taking into account the ART treatment methods and the type of infertility.
STUDY FUNDING/COMPETING INTEREST(s)
This work was supported by the National Agency of Biomedicine. The authors have no competing interests to disclose.
TRIAL REGISTRATION NUMBER
NA.
What are the risk factors for prematurity other than intrauterine growth restriction in singletons after IVF?
Data were collected from a national registry, based on an observational prospective ...cohort of 30,737 live births after assisted reproductive technology (fresh embryo transfers: n = 20,932 and frozen embryo transfer FET n = 9805) between 2014 and 2015. A population of not-small for gestational age singletons conceived after fresh embryo transfers and FET, and their parents, was selected. Data on a number of variables were collected, including type of infertility, number of oocytes retrieved and vanishing twins.
Preterm birth occurred in 7.7% (n = 1607) of fresh embryo transfers and 6.2% (n = 611) of frozen–thawed embryo transfers (P < 0.0001; adjusted odds ratio aOR = 1.34 1.21–1.49). Endometriosis and vanishing twin increased the risk of preterm birth after fresh embryo transfer (P < 0.001; aOR 1.32 and 1.78, respectively). Polycystic ovaries or more than 20 oocytes retrieved also increased preterm birth risk (aOR 1.31 and 1.30; P = 0.003 and P = 0.02, respectively); large oocyte cohort (>20) was no longer associated with the risk of prematurity in FET.
Endometriosis remains a risk for prematurity even in the absence of intrauterine growth retardation, which suggests a dysimmune effect. Large oocyte cohorts obtained by stimulation, without clinical polycystic ovary syndrome diagnosed before attempts, do not affect FET outcomes, reinforcing the idea of a phenotypic difference in the clinical presentation of polycystic ovary syndrome.
BACKGROUND: A case of idiopathic primary infertility was attributed to a block in oocyte meiosis affecting the transition between metaphase I and metaphase II. METHODS AND RESULTS: A couple suffering ...unexplained primary infertility was unsuccessfully treated by various means of assisted reproductive technology. After four unsuccessful pregnancy attempts using intrauterine inseminations (IUI), IVF was attempted (all oocytes remained unfertilized), followed by an ICSI cycle. None of the retrieved oocytes expelled the polar body, and therefore were not injected. The failure of these assisted reproduction cycles was, in both cases, due to the immaturity of the oocytes recovered. Cytogenetic analysis of the oocytes retrieved for ICSI provided evidence of meiotic arrest. Using cytogenetic staging criteria we were able to show that this arrest occurred between metaphase I and anaphase I. CONCLUSIONS: Meiotic blocks affecting oocytes have already been described for various mammals. We discuss here mechanisms that might be involved in this possibly inherited disorder in humans, and ways in which our knowledge of them could be increased.
Obtaining an adequate number of high-quality oocytes is a major challenge in controlled ovarian hyperstimulation (COH). To date, a range of hormonal and clinical parameters have been used to optimize ...COH but none have significant predictive value. This variability could be due to the genetic predispositions of single-nucleotide polymorphisms (SNPs). Here, we assessed the individual and combined impacts of thirteen SNPs that reportedly influence the outcome of in vitro fertilisation (IVF) on the ovarian response to rFSH stimulation for patients undergoing intracytoplasmic sperm injection program (ICSI).
Univariate analysis revealed that only FSHR, ESR2 and p53 SNPs influenced the number of mature oocytes. The association was statistically significant for FSHR (p=0.0047) and ESR2 (0.0017) in the overall study population and for FSHR (p=0.0009) and p53 (p=0.0048) in subgroup that was more homogeneous in terms of clinical variables. After Bonferroni correction and a multivariate analysis, only the differences for FSHR and ESR2 polymorphisms were still statistically significant. In a multilocus analysis, only the FSHR and AMH SNP combination significantly influenced oocyte numbers in both population (p<0.01).
We confirmed the impact of FSHR and ESR2 polymorphisms on the IVF outcome. Furthermore, we showed for the first time that a p53 polymorphism (which is already known to impact embryo implantation) could influence the ovarian response. However, given that this result lost its statistical significance after multivariate analysis, more data are needed to draw firm conclusions. Only the FSHR and AMH polymorphism combination appears to influence mature oocyte numbers but this finding also needs to be confirmed.
A 13 gene polymorphisms: FSHR(Asn680Ser), p53(Arg72Pro), AMH(Ile49Ser), ESR2(+1730G>A), ESR1(-397T>C), BMP15(-9C>G), MTHFR1(677C>T), MTHFR2(1298A>C), HLA-G(-725C>G), VEGF(+405G>C), TNFα(-308A>G), AMHR(-482 A>G), PAI-1 (4 G/5 G), multiplex PCR assay was designed to genotype women undergoing ICSI program. We analyzed the overall study population (n=427) and a subgroup with homogeneous characteristics (n=112).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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