Over the past 40 years access and effectiveness of assisted reproductive technologies (ART) have increased, and to date more than 8 million children have been conceived after ART globally. Most pre...

Perinatal outcome in children born after assisted reproductive technologies.

This systematic review of literature and meta-analysis of observational studies reports on perinatal outcomes after frozen embryo transfer (FET) The aim was to determine whether natural cycle frozen embryo transfer (NC-FET) in singleton pregnancies conceived after IVF decreased the risk of adverse perinatal outcomes compared with artificial cycle frozen embryo transfer (AC-FET) Thirteen cohort studies, including 93,201 cycles, met the inclusion criteria NC-FET was associated with a lower risk of hypertensive disorders in pregnancy (HDP) (RR 061, 95% CI 050 to 073), preeclampsia (RR 047, 95% CI 042 to 053), large for gestational age (LGA) (RR 093, 95% CI 090 to 096) and macrosomia (RR 082, 95% CI 069 to 097) compared with AC-FET No significant difference was found in the risk of gestational hypertension and small for gestational age Secondary outcomes assessed were the risk of preterm birth (RR 083, 95% CI 079 to 088); post-term birth (RR 048, 95% CI 029 to 080); low birth weight (RR 084, 95% CI 080 to 089); caesarean section (RR 084, 95% CI 077 to 091); postpartum haemorrhage (RR 039, 95% CI 035 to 045); placental abruption (RR 061, 95% CI 038 to 098); and placenta accreta (RR 018, 95% CI 010 to 033) All were significantly lower with NC-FET compared with AC-FET In assessing safety, NC-FET significantly decreased the risk of HDP, preeclampsia, LGA, macrosomia, preterm birth, post-term birth, low birth weight, caesarean section, postpartum haemorrhage, placental abruption and placenta accreta Further randomized controlled trials addressing the effect of NC-FET and AC-FET on maternal and perinatal outcomes are warranted Clinicians should carefully monitor pregnancies achieved by FET in artificial cycles prenatally, during labour and postnatally

Lower risk of adverse perinatal outcomes in natural versus artificial frozen-thawed embryo transfer cycles: a systematic review and meta-analysis.

Management of male factor infertility: position statement from the Italian Society of Andrology and Sexual Medicine (SIAMS)

Is there an association between the different endometrial preparation protocols for frozen embryo transfer (FET) and obstetric and perinatal outcomes?Programmed FET protocols were associated with a significantly higher risk of hypertensive disorders of pregnancy (HDP), pre-eclampsia (PE), post-partum hemorrhage (PPH) and cesarean section (CS) when compared with natural FET protocols.An important and growing source of concern regarding the use of FET on a wide spectrum of women, is represented by its association with obstetric and perinatal complications. However, reasons behind these increased risks are still unknown and understudied.Systematic review with meta-analysis. We systematically searched PubMed, MEDLINE, Embase and Scopus, from database inception to 1 November 2021. Published randomized controlled trials, cohort and case control studies were all eligible for inclusion. The risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. The quality of evidence was also evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.Studies were included only if investigators reported obstetric and/or perinatal outcomes for at least two of the following endometrial preparation protocols: programmed FET cycle (PC-FET) (i.e. treatment with hormone replacement therapy (HRT)); total natural FET cycle (tNC-FET); modified natural FET cycle (mNC-FET); stimulated FET cycle (SC-FET).Pooled results showed a higher risk of HDP (12 studies, odds ratio (OR) 1.90; 95% CI 1.64-2.20; P < 0.00001; I2 = 50%) (very low quality), pregnancy-induced hypertension (5 studies, OR 1.46; 95% CI 1.03-2.07; P = 0.03; I2 = 0%) (very low quality), PE (8 studies, OR 2.11; 95% CI 1.87-2.39; P < 0.00001; I2 = 29%) (low quality), placenta previa (10 studies, OR 1.27; 95% CI 1.05-1.54; P = 0.01; I2 = 8%) (very low quality), PPH (6 studies, OR 2.53; 95% CI 2.19-2.93; P < 0.00001; I2 = 0%) (low quality), CS (12 studies, OR 1.62; 95% CI 1.53-1.71; P < 0.00001; I2 = 48%) (very low quality), preterm birth (15 studies, OR 1.19; 95% CI 1.09-1.29; P < 0.0001; I2 = 47%) (very low quality), very preterm birth (7 studies, OR 1.63; 95% CI 1.23-2.15; P = 0.0006; I2 = 21%) (very low quality), placenta accreta (2 studies, OR 6.29; 95% CI 2.75-14.40; P < 0.0001; I2 = 0%) (very low quality), preterm premature rupture of membranes (3 studies, OR 1.84; 95% CI 0.82-4.11; P = 0.14; I2 = 61%) (very low quality), post-term birth (OR 1.90; 95% CI 1.25-2.90; P = 0.003; I2 = 73%) (very low quality), macrosomia (10 studies, OR 1.18; 95% CI 1.05-1.32; P = 0.007; I2 = 45%) (very low quality) and large for gestational age (LGA) (14 studies, OR 1.08; 95% CI 1.01-1.16; P = 0.02; I2 = 50%) (very low quality), in PC-FET pregnancies when compared with NC (tNC + mNC)-FET pregnancies. However, after pooling of ORs adjusted for the possible confounding variables, the endometrial preparation by HRT maintained a significant association in all sub-analyses exclusively with HDP, PE, PPH (low quality) and CS (very low quality).The principal limitation concerns the heterogeneity across studies in: (i) timing and dosage of HRT; (ii) embryo stage at transfer; and (iii) inclusion of preimplantation genetic testing cycles. To address it, we undertook subgroup analyses by pooling only ORs adjusted for a specific possible confounding factor.Endometrial preparation protocols with HRT were associated with worse obstetric and perinatal outcomes. However, because of the methodological weaknesses, recommendations for clinical practice cannot be made. Well conducted prospective studies are thus warranted to establish a safe endometrial preparation strategy for FET cycles aimed at limiting superimposed risks in women with an 'a priori' high-risk profile for obstetric and perinatal complications.None.CRD42021249927. 

OUP accepted manuscript

STUDY QUESTION
Is there an association between the different endometrial preparation protocols for frozen embryo transfer (FET) and obstetric and perinatal outcomes?


SUMMARY ANSWER
Programmed FET protocols were associated with a significantly higher risk of hypertensive disorders of pregnancy (HDP), pre-eclampsia (PE), post-partum hemorrhage (PPH) and cesarean section (CS) when compared with natural FET protocols.


WHAT IS KNOWN ALREADY
An important and growing source of concern regarding the use of FET on a wide spectrum of women, is represented by its association with obstetric and perinatal complications. However, reasons behind these increased risks are still unknown and understudied.


STUDY DESIGN, SIZE, DURATION
Systematic review with meta-analysis. We systematically searched PubMed, MEDLINE, Embase and Scopus, from database inception to 1 November 2021. Published randomized controlled trials, cohort and case control studies were all eligible for inclusion. The risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. The quality of evidence was also evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.


PARTICIPANTS/MATERIALS, SETTING, METHODS
Studies were included only if investigators reported obstetric and/or perinatal outcomes for at least two of the following endometrial preparation protocols: programmed FET cycle (PC-FET) (i.e. treatment with hormone replacement therapy (HRT)); total natural FET cycle (tNC-FET); modified natural FET cycle (mNC-FET); stimulated FET cycle (SC-FET).


MAIN RESULTS AND THE ROLE OF CHANCE
Pooled results showed a higher risk of HDP (12 studies, odds ratio (OR) 1.90; 95% CI 1.64-2.20; P < 0.00001; I2 = 50%) (very low quality), pregnancy-induced hypertension (5 studies, OR 1.46; 95% CI 1.03-2.07; P = 0.03; I2 = 0%) (very low quality), PE (8 studies, OR 2.11; 95% CI 1.87-2.39; P < 0.00001; I2 = 29%) (low quality), placenta previa (10 studies, OR 1.27; 95% CI 1.05-1.54; P = 0.01; I2 = 8%) (very low quality), PPH (6 studies, OR 2.53; 95% CI 2.19-2.93; P < 0.00001; I2 = 0%) (low quality), CS (12 studies, OR 1.62; 95% CI 1.53-1.71; P < 0.00001; I2 = 48%) (very low quality), preterm birth (15 studies, OR 1.19; 95% CI 1.09-1.29; P < 0.0001; I2 = 47%) (very low quality), very preterm birth (7 studies, OR 1.63; 95% CI 1.23-2.15; P = 0.0006; I2 = 21%) (very low quality), placenta accreta (2 studies, OR 6.29; 95% CI 2.75-14.40; P < 0.0001; I2 = 0%) (very low quality), preterm premature rupture of membranes (3 studies, OR 1.84; 95% CI 0.82-4.11; P = 0.14; I2 = 61%) (very low quality), post-term birth (OR 1.90; 95% CI 1.25-2.90; P = 0.003; I2 = 73%) (very low quality), macrosomia (10 studies, OR 1.18; 95% CI 1.05-1.32; P = 0.007; I2 = 45%) (very low quality) and large for gestational age (LGA) (14 studies, OR 1.08; 95% CI 1.01-1.16; P = 0.02; I2 = 50%) (very low quality), in PC-FET pregnancies when compared with NC (tNC + mNC)-FET pregnancies. However, after pooling of ORs adjusted for the possible confounding variables, the endometrial preparation by HRT maintained a significant association in all sub-analyses exclusively with HDP, PE, PPH (low quality) and CS (very low quality).


LIMITATIONS, REASONS FOR CAUTION
The principal limitation concerns the heterogeneity across studies in: (i) timing and dosage of HRT; (ii) embryo stage at transfer; and (iii) inclusion of preimplantation genetic testing cycles. To address it, we undertook subgroup analyses by pooling only ORs adjusted for a specific possible confounding factor.


WIDER IMPLICATIONS OF THE FINDINGS
Endometrial preparation protocols with HRT were associated with worse obstetric and perinatal outcomes. However, because of the methodological weaknesses, recommendations for clinical practice cannot be made. Well conducted prospective studies are thus warranted to establish a safe endometrial preparation strategy for FET cycles aimed at limiting superimposed risks in women with an 'a priori' high-risk profile for obstetric and perinatal complications.


STUDY FUNDING/COMPETING INTEREST(S)
None.


REGISTRATION NUMBER
CRD42021249927.

Obstetric and perinatal outcomes following programmed compared to natural frozen-thawed embryo transfer cycles: a systematic review and meta-analysis.

In women with singleton pregnancies conceived after assisted reproductive technologies, does the in vitro fertilization with oocyte donation (IVF-OD) affect the perinatal and maternal outcomes compared to autologous in vitro fertilization (IVF-AO)? Systematic review and meta-analysis of studies comparing perinatal and maternal outcomes in singleton pregnancies resulting from IVF-OD versus IVF-AO. An electronic literature search in Pubmed, MEDLINE, and Cochrane database was performed. The main outcome measures were hypertensive disorders in pregnancy, preeclampsia, severe preeclampsia, pregnancy-induced hypertension, preterm birth, early preterm birth, low birth weight, and very low birth weight. Twenty-three studies were included. IVF-OD is associated with a higher risk of hypertensive disorders in pregnancy (OR 2.63, 2.17–3.18), preeclampsia (OR 2.64; 2.29–3.04), severe preeclampsia (OR 3.22; 2.30–4.49), pregnancy-induced hypertension (OR 2.16; 1.79–2.62), preterm birth (OR 1.57; 1.33–1.86), early preterm birth (OR 1.80; 1.51–2.15), low birth weight (OR 1.25, 1.20–1.30), very low birth weight (OR 1.37, 1.22–1.54), gestational diabetes (OR 1.27; 1.03–1.56), and cesarean section (OR 2.28; 2.14–2.42). There was no significant difference in the risk of preterm birth or low birth weight when adjusted for preeclampsia. IVF-OD patients should be considered an independent risk factor for some adverse perinatal outcomes, mainly hypertensive disorders in pregnancy, preeclampsia, and severe preeclampsia. Immunological and hormonal aspects may be involved in these results, and further research focusing in the etiopathogenesis of these pathologies are needed.

Risk of adverse perinatal outcomes after oocyte donation: a systematic review and meta-analysis

BACKGROUND The impact of human papillomavirus (HPV) on male fertility and associated reproductive outcomes has not been clarified. OBJECTIVES To elucidate the prevalence of seminal HPV infection and assess the associated effects on seminal parameters, male infertility, and reproductive outcomes. MATERIALS AND METHODS A systematic review and meta-analysis was performed in accordance with PRISMA guidelines. A search was performed using PubMed, MEDLINE, SCOPUS, and Cochrane databases. Studies published until November 2019 were included. HPV prevalence, risk of infertility, seminal parameters, and reproductive outcomes were evaluated among the general population and infertile men. RESULTS Fifty studies met the inclusion criteria. The prevalence of seminal HPV infection is significantly higher in infertile compared to the general population (20.9% versus 8.2%). A significant association between seminal HPV infection and male infertility (OR 3.30, 95% CI 1.87-5.84), even when adjusting for female infertility (OR 3.02, 95% CI = 2.11-4.33) was founded. In addition, HPV infection is related to a significant decrease in progressive motility (DM -10.35, IC -13.75, -6.96), a low sperm morphology score (DM -2.46, 95% CI -3.83, -1.08), and a significant increase in the sperm DNA fragmentation index (7.24, 95% CI 4.44.10.03) compared with HPV-negative patients. It was also observed an increased risk of miscarriage (OR 5.13, 95% CI 2.40,10.94), and a reduced chance of ongoing pregnancy (OR 0.33, IC 95% 0.13,0,82) in patients undergoing ART with seminal HPV infection. DISCUSSION Infertile men have a higher prevalence of seminal HPV infection compared to the general population, regardless of the HPV genotype detected. CONCLUSIONS HPV in semen may have an impact in sperm quality and reproductive outcomes. Additional well-designed studies are warranted to improve the quality of evidence.

Seminal human papillomavirus infection and reproduction: a systematic review and meta-analysis.

Transferencia de embriones congelados y riesgo de parto prematuro: estudio de la cohorte española


 
 
 Are the ovarian response to controlled ovarian stimulation (COS) and embryo development after in vitro fertilization (IVF) affected by SARS-CoV-2 infection and immunization?
 
 
 
 Both SARS-CoV-2 infection and SARS-CoV-2 mRNA or inactivated vaccinations do not affect ovarian responsiveness to COS or embryo development following IVF.
 
 
 
 SARS-CoV-2 infects the target cell by binding to angiotensin-converting enzyme 2 (ACE2) via its surface spike protein. ACE2 receptors are present in the vagina, uterus, fallopian tubes, and ovaries of the female reproductive system. They regulate ovarian steroidogenesis, follicular development, oocyte maturation, and follicle atresia. The virus downregulates ACE2 levels, resulting in decreased conversion of Angiotensin II (ANGII) to Ang (1-7) and increased accumulation of (ANGII). This may impair reproductive fertility. However, initial studies conclude that both SARS-CoV-2 infection and vaccination would not affect reproductive outcomes, but it is necessary to develop new studies that confirm their applicability.
 
 
 
 A retrospective multicentric cohort study of 428 patients who underwent COS for oocyte donation between January 1st, 2018 and July 31th, 2022 were screened for eligibility and followed up to September 18th, 2022. Oocyte donation cycles were utilized because this model is an excellent choice for controlling known female characteristics
 
 
 
 Eligibility criteria were donors between 18 to 32 years. Patients were categorized into the vaccinated group if they had received SARS-CoV-2 vaccines (BNT162b2 mRNA Pfizer-Biontech, mRNA-1273 Moderna or inactivated SARS-CoV-2 vaccine Sinovac). The control group was chosen from medical records before March 2020 ensure they were neither infected or vaccinated. Demographic, cycle characteristics, and laboratory outcomes were compared. Normally, distributed data were compared across groups by univariate ANOVA. All P-values were considered significant at < 0.05.
 
 
 
 In total, 428 patients were included in the study, with 12 recovering from SARS–CoV-2 infection (Group 1), 92 reporting vaccination (Group 2), and 324 patients who underwent COS before March 2020 assigned to the non-exposed group (Group 3).
 The mean time from recovery to oocyte aspiration was 122 days (range 39-315 days) and 213 days from the first vaccine dose to oocyte aspiration (range 17–249 days).
 The study's participants had an average age of 24.8 years. Age was found to be normally distributed and did not differ significantly between the three groups (P-value 0,953). Similarly, ovarian reserve markers, as measured by AFC and AMH, did not differ between groups (P-values of 0,787 and 0,423 respectively).
 No significant differences were observed regarding stimulation duration and total gonadotropin dose. The number of retrieved oocytes, MII oocytes, fertilized oocytes, and good-quality day 5 embryos were also similar between the three groups. Comparing oocyte retrieval rate, mature oocyte rate, normal fertilization rate, and blastocyst formation rate consistently revealed no statistically significant differences.
 
 
 
 The main limitation is its retrospective design. Other limitations include the small sample size of recovered patients, the absence of sperm analyses, and data of live birth rates and neonatal outcomes.
 
 
 
 SARS-CoV-2 infection and vaccination seem unrelated to detrimental effects on ovarian response or embryo development. These findings contribute to the growing body evidence that supports vaccination in women trying to conceive. Further prospective studies with larger cohort sizes and longer follow-ups are warranted to validate our conclusion.
 
 
 
 NCT05562479


/pdf/p-466-the-effect-of-sars-cov-2-infection-or-vaccination-on-1zcnsrvs.pdf

P-466 The effect of SARS-CoV-2 infection or vaccination on controlled ovarian stimulation and in vitro fertilization: A multicenter retrospective cohort study

Jose Moreno-Sepulveda

Papers

Risk of adverse perinatal outcomes after oocyte donation: a systematic review and meta-analysis

Seminal human papillomavirus infection and reproduction: a systematic review and meta-analysis.

Lower risk of adverse perinatal outcomes in natural versus artificial frozen-thawed embryo transfer cycles: a systematic review and meta-analysis.

Transferencia de embriones congelados y riesgo de parto prematuro: estudio de la cohorte española

P-466 The effect of SARS-CoV-2 infection or vaccination on controlled ovarian stimulation and in vitro fertilization: A multicenter retrospective cohort study