Undetected, natural conception pregnancies in luteal phase stimulations-case series and review of literature.

STUDY QUESTION: What is the risk of an undetected natural conception pregnancy during luteal phase ovarian stimulation, and how does it impact the pregnancy's course? SUMMARY ANSWER: The risk for an undetected, natural conception pregnancy in luteal phase ovarian stimulation is low and it appears that ovarian stimulation is unlikely to harm the pregnancy. WHAT IS KNOWN ALREADY: Random start ovarian stimulation appears to be similarly effective as early follicular stimulation start; and it allows ovarian stimulation to be started independent of the cycle day and throughout the cycle, in accordance with the patients' and clinics' schedule as long as there is no intention of a fresh embryo transfer in the same cycle. Starting ovarian stimulation in the luteal phase bears the possibility of an-at the timepoint of stimulation start-undetected, natural conception pregnancy that has already occurred. There is scarce data on the incidence of this event as well as on the possible implications of ovarian stimulation on the course of an existing pregnancy. STUDY DESIGN, SIZE, DURATION: This retrospective observational study, performed between June 2017 and January 2024, analyzed luteal phase stimulations, in which a natural conception pregnancy was detected during the ovarian stimulation treatment for IVF/ICSI. Luteal phase stimulation was defined as ovarian stimulation started after ovulation and before the next expected menstrual bleeding, with a serum progesterone (P4) level of >1.5 ng/ml on the day of stimulation start or 1 day before. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women who underwent a luteal phase ovarian stimulation in a tertiary referral ART center. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 488 luteal phase stimulation cycles were included in the analysis. Luteal phase stimulation was only started after a negative serum hCG measurement on the day or 1 day before commencement of ovarian stimulation. Ten patients (2.1%) had an undetected natural conception pregnancy at the time of luteal phase stimulation start. Eight of these patients underwent an ovarian stimulation in a GnRH-antagonist protocol and two in a progestin-primed stimulation protocol (PPOS). Recombinant FSH was used as stimulation medication for all patients, the patients with a PPOS protocol received additional recombinant LH. One pregnancy (0.2%) was detected after the oocyte retrieval, the other nine pregnancies were detected either due to persistent high serum progesterone levels or due to an increasing progesterone level after an initial decrease before oocyte retrieval. In the cycles with an undetected natural conception pregnancy, the median number of stimulation days was 8 days (range: 6-11 days) and median serum hCG at detection of pregnancy was 59 IU hCG (range: 14.91-183.1). From 10 patients with a pregnancy, three patients delivered a healthy baby, two patients had ongoing pregnancies at the time of summarizing the data, three patients had biochemical pregnancies (patient age: 30, 39, and 42 years), one patient had an ectopic pregnancy which required a salpingectomy, and one patient (age: 34 years) had an early pregnancy loss. LIMITATIONS, REASONS FOR CAUTION: The retrospective study design and the small sample size can limit the accuracy of the estimates. WIDER IMPLICATIONS OF THE FINDINGS: Overall, there is a small risk of undetected natural conception pregnancies when luteal phase stimulation is undertaken. It appears that there are no adverse effects through either direct effect on the embryo or indirectly through a detrimental effect on the corpus luteum function on the pregnancy in our cohort. STUDY FUNDING/COMPETING INTEREST(S): This study did not receive funding. The authors declare that there is no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Corrigendum: Trends in acupuncture for infertility: a scoping review with bibliometric and visual analysis.

[This corrects the article DOI: 10.3389/fendo.2024.1351281.].

Trends in acupuncture for infertility: a scoping review with bibliometric and visual analysis.

Background: Unexplained recurrent implantation failure and the high cost of assisted reproductive techniques for those experiencing infertility have increasingly resulted in the use of acupuncture. However, the trends and research status of acupuncture on infertility resulting in natural conception have not been systematically summarized. This scoping review and knowledge graph analysis aimed to summarize existing clinical studies on acupuncture for infertility that resulted in natural conception. Methods: Seven databases, namely, PubMed, Embase, the Cochrane Library, CNKI, VIP, Wanfang Data, and SinoMed, were searched up to August 2023 (updated on 1 April). Two authors independently identified related clinical studies and systematic reviews, and extracted data from included studies on acupuncture for infertility; any discrepancies were resolved by discussion or judged by a third author. A meta-analysis was conducted based on randomized controlled trials (RCTs), and data were synthesized using risk ratios with 95% confidence intervals. Results: Of the 310 articles meeting the inclusion criteria, 274 were primary studies, 7 were systematic reviews, and 29 were case reports. Reported adverse events included mild ovarian irritation and early signs of miscarriage. Out of the 274 primary studies, there were 40 (14.60%) cases of male infertility and 234 (85.40%) cases of female infertility. Current research highlights on acupuncture for infertility focused on female infertility caused by polycystic ovary syndrome, ovulation disorder, and luteinized unruptured follicle syndrome (LUFS), while acupuncture for male infertility was a hotspot in the early research stage. The meta-analysis also suggested that acupuncture was more effective than human chorionic gonadotropin (HCG) [RR = 1.89, 95% CI (1.47, 2.42), 11 RCTs, 662 participants]. Acupuncture combined with HCG was comparable to HCG [RR = 2.33, 95% CI (1.53, 3.55), four RCTs, 259 participants]. Compared with no treatment, acupuncture resulted in a higher pregnancy rate [RR = 22.12, 95% CI (1.39, 353.09), one RCT, 47 participants]. There was no statistical difference between acupuncture combined with HCG plus letrozole and HCG plus letrozole [RR = 1.56, 95% CI (0.84, 2.89), one RCT, 84 participants]. Conclusion: Current research highlights on acupuncture for infertility resulting in natural conception focused on female infertility caused by polycystic ovary syndrome, ovulation disorder, and LUFS, while studies on male infertility and female infertility caused by blockage in the fallopian tube, thin endometrium, and other factors were insufficient. Well-designed confirmatory clinical studies are still needed as the research hypotheses of most studies were unclear.

Evaluating prognosis in unexplained infertility.

IMPORTANCE: The diagnosis of unexplained infertility presents a dilemma as it signifies both uncertainty about the cause of infertility and the potential for natural conception. Immediate treatment of all would result in overtreatment. Prediction models estimating the likelihood of natural conception and subsequent live birth can guide treatment decisions. OBJECTIVE: To evaluate if in couples with unexplained infertility, prediction models are effective in guiding treatment decisions. EVIDENCE REVIEW: This review examines 25 studies that assess prediction models for natural conception in couples with unexplained infertility in terms of derivation, validation, and impact analysis. FINDINGS: The largest prediction models have been integrated in the synthesis models of Hunault, which includes female age and infertility duration, having been pregnant before and motile sperm percentage. Despite its limited discriminative capacity, this model demonstrates excellent calibration. Importantly, the impact of the Hunault model has been evaluated in randomized clinical trials, and shows that in couples with unexplained infertility and 12-month natural conception chances exceeding 30%, immediate treatment with intrauterine insemination (IUI) and controlled ovarian hyperstimulation is not better than expectant management for 6 months. Below the threshold of 30%, treatment with IUI is superior over expectant management, but immediate in vitro fertilization was not better than IUI. CONCLUSION: In couples with unexplained infertility and a good prognosis for natural conception, treatment can be delayed, whereas in couples with a poor prognosis, immediate treatment (with IUI-controlled ovarian hyperstimulation) is warranted. RELEVANCE: These data indicate that in couples with unexplained infertility, integration of prediction models into clinical decision making can optimize treatment selection and maximize fertility outcomes while limiting unnecessary treatment.

Case-controlled study of tuberculosis in in-vitro fertilisation-embryo transfer and natural pregnancy.

OBJECTIVE: To improve the understanding of the clinical features and imaging characteristics of pregnant women with and without in-vitro fertilisation-embryo transfer combined with pulmonary tuberculosis (TB). METHODS: A retrospective analysis was conducted involving 50 patients with pregnancy who had pulmonary TB and were admitted to the Third People's Hospital of Kunming (China) between 1 January 2017 and 31 December 2021. These patients were divided into an in-vitro fertilisation and embryo transfer (IVF-ET) conception group and a natural conception group according to the conception method. The clinical and imaging data were then collected and compared. RESULTS: The mean age of the IVF-ET group (n = 13, 31.85 ± 5.84 years) was higher than in the natural conception group (n = 37, 27.05 ± 5.5 years). The proportions of fever, haematogenous TB and extrapulmonary TB in the IVF-ET group (92.31%, 84.62% and 76.92%, respectively) were higher than those in the natural conception group (40.54%,16.22%,27.03%,respectively). The percentage of patients with pregnancy who had intracranial TB (76.9%) in the IVF-ET group was higher than in the natural conception group (10.8%). The percentage of pregnancy terminations in the IVF-ET conception group (84.62%) was higher than in the natural conception group (48.65%). All the above results had statistically significant differences (p < 0.05). CONCLUSION: Overall, IVF-ET conception combined with extensive pulmonary TB lesions lead to heavy systemic toxic symptoms, severe disease and poor pregnancy outcomes. Therefore, screening for TB prior to performing IVF-ET is recommended.

The impact of metabolic surgery on natural conception rates in women with infertility, obesity and polycystic ovary syndrome: a retrospective study.

BACKGROUND: Women with obesity and polycystic ovary syndrome (OPOS) are at high risk for infertility. However, the reproductive effects of metabolic surgery on women with infertility and OPOS have not been fully elucidated. OBJECTIVES: We investigated the natural conception rates after metabolic surgery, and the variables associated with infertility in women with OPOS. SETTING: Shanghai Sixth People's Hospital, Shanghai, China. METHODS: This study included 72 women with infertility and OPOS who underwent metabolic surgery and were followed up for 4 years after surgery. Finally, 54 patients completed the study. Reproductive outcomes were assessed, along with changes in anthropometric parameters and metabolic indices before and 1 year after surgery (prepregnancy). Logistic regression analysis was used to identify variables influencing natural conception and delivery outcomes. RESULTS: After metabolic surgery, 35 patients (64.8%) became pregnant naturally, while 16 were still unable to conceive naturally. Preoperative body mass index (BMI) tended to be lower in the natural conception group than in the no natural conception group (38.9 ± 6.9 versus 43.6 ± 11.0 kg/m2, P = .070) and there were no significant differences in weight loss between the 2 groups after surgery. Logistic regression analysis showed that the BMI 1 year after surgery (prepregnancy) was an independent predictor of natural conception, and receiver operating characteristic analysis showed that a BMI of 27.0 kg/m2 was the optimal cutoff for predicting successful natural conception after surgery. CONCLUSIONS: Metabolic surgery can improve fertility in women with OPOS. Patients with a BMI < 27.0 kg/m2 1 year after surgery (prepregnancy) are more likely to become pregnant naturally and give birth.

Design and baseline characteristics of a population-based birth cohort in Shanghai / 上海预防医学

ObjectiveTo introduce the basic design， development plan and objectives of a population-based birth cohort in Shanghai， and further present the main data and baseline characteristics of enrolled participants in the cohort， and to provide key information for reproductive health-related studies. MethodsThe Shanghai population-based birth cohort initiated on January 1， 2005， included newborns born in Shanghai every year and their parents， and collected information on reproductive health， reproductive treatment， birth characteristics， growth and development status， as well as the incidence， treatment and death of diseases by employing data linkage technology and investigations. This formed a birth cohort spanning the entire life cycle. ResultsAs of October 2022， a total of 2 978 538 newborns and their parents were included in the cohort. Among them， 2 905 135 （97.54%） were naturally conceived （NC）， and 73 403 （2.46%） were born through assisted reproductive technologies （ART）. The average age of parents was （32.56±4.12） years old for females and （34.62±5.34） years old for males in the ART group， which was higher than （28.02±4.71） years and （30.07±5.54） years for parents in the NC group. Among parents， females and males aged 30 and above accounted for 77.12% and 85.08%， respectively， which were higher than that of parents （35.28% for females and 49.66% for males） in the NC group. Furthermore， the percentage of parents with a college degree or above in the ART group was 73.23% for females and 73.66% for males， which were higher than those in the NC group （49.98% and 50.91%， respectively）. The multiple births rate in the ART group was 33.81%， which was higher than that in the NC group （1.88%）. The incidence of premature birth and low birth weight in the ART group were 24.47% and 19.08%， respectively， which was higher than that in the NC group （5.47% and 3.73%）. ConclusionThe comprehensive collection of reproductive health-related information in the birth cohort in Shanghai can provide essential resources to determine the influence of genetics， environment， reproductive treatment and other related factors on the health of offspring after birth.

Clinical Efficacy of TCM Multi-channel Intervention Plus Antagonist Regimen on Ovarian Function，TCM Syndromes and Natural Conception in Poor Ovarian Responders Undergoing IVF-ET / 中国实验方剂学杂志

ObjectiveTo objectively analyze the effects of traditional Chinese Medicine （TCM） multi-channel intervention on the ovarian function，TCM syndromes and natural conception of poor ovarian responders（kidney-Yin deficiency，liver depression and blood stasis pattern） who planned to receive another in vitro fertilization embryo transfer（IVF-ET）antagonist regimen. MethodThe 128 low-prognosis patients （kidney Yin deficiency，liver depression and blood stasis pattern） who attended the West China Second University Hospital， Sichuan University and the Hospital of Chengdu University of Traditional Chinese Medicine from August 2020 to February 2023 and met the inclusion criteria were selected，and then divided into the treatment group and the control group according to the random number table，with 64 patients in each group. The control group was treated with oral dehydroepiandrosterone（DHEA），while the treatment group was treated with multi-channel TCM（oral TCM decoction + auricular point sticking + Bushen Huoxue prescription through retention enema）. After 3 menstrual cycles，the relevant indicators for ovarian function evaluation，TCM syndrome scores and natural conception were collected from both groups. ResultCompared with the situation before treatment，the basal follicle stimulating hormone（bFSH），bFSH/basal luteinizing hormone（bLH），basal estradiol（bE2），antral follicle count（AFC），the number of oocytes obtained，the number of normal fertilization，the number of superior embryos and TCM syndrome scores in the treatment group were improved after treatment（P<0.05，P<0.01）. For the control group， the bFSH/bLH and TCM syndrome scores were increased after treatment（P<0.05）， while the bFSH，bFSH/bLH，bE2，AFC，the number of oocytes obtained，the number of normal fertilization，and the number of superior embryos showed no significant difference after treatment. Compared with the control group after treatment，bFSH，bFSH/bLH，bE2，AFC，the number of normal fertilization，the number of superior embryos and TCM syndrome scores in the treatment group were better （P<0.05，P<0.01），while there was no significant difference in the number of oocytes obtained. After treatment，there were 3 cases of natural conception in the treatment group，while there were no natural conception in the control group. ConclusionFor patients with poor ovarian response and kidney Yin deficiency，liver depression and blood stasis pattern，multi-channel intervention of TCM plus the antagonist regimen can reduce bFSH，bFSH/bLH values，improve the levels of bE2，increase AFC，the number of oocytes obtained，the number of normal fertilization and the number of superior embryos，improve ovarian function，menstruation and TCM syndromes，improve their quality of life，and even enable some patients to get pregnant naturally before re-progression and improve their pregnancy outcome.

Perinatal Outcomes of Monochorionic Twin Pregnancies Conceived Naturally Versus through Assisted Reproductive Techniques.

Objective: It has been reported that monochorionic twin pregnancies conceived through assisted reproductive techniques (ART) display a higher risk of second-trimester miscarriage, cesarean delivery, and neonatal death than those conceived naturally. The aim of this study was to compare the perinatal outcomes of monochorionic diamniotic (MCDA) twin pregnancies conceived naturally and through ART in a tertiary hospital. Methods: This was a retrospective cohort study of all MCDA twin pregnancies that received obstetric care and delivered at La Fe University and Polytechnic Hospital between 2015 and 2021. MCDA pregnancies that were referred to the tertiary hospital for specialized management, follow-up, and delivery were also included. The study was approved by The Health Research Institute Hospital La Fe (IIS La Fe). Results: Among the 184 MCDA pregnancies, 149 (81%) had a natural conception, and 35 (19%) were conceived through ART. Patients with an MCDA pregnancy who conceived through ART had a significantly older maternal age (38.0 [35.5-42.5] vs. 32.0 [29.0-36.0], p < 0.001) and an elevated rate of nulliparity (80.0% vs. 50.3%, p = 0.001). Regarding pregnancy complications, MCDA pregnancies through ART were associated with a significantly higher incidence of gestational diabetes (22.9% vs. 2.7%, p < 0.001), hypertensive disorders during pregnancy (22.9% vs. 9.4%, p = 0.04), and other pregnancy complications such as threatened labor or preterm prelabor rupture of membranes (14.3% vs. 36.2%, p = 0.015), than naturally conceived MCDA pregnancies. No differences were found in the incidence of twin-to-twin transfusion syndrome (20% vs. 33.6%, p = 0.155). MCDA pregnancies through natural conception had a greater rate of vaginal delivery than MCDA through ART (16.8% vs. 2.9%, p = 0.032). When adjusted for confounding factors, MCDA pregnancies through ART were only more likely to develop gestational diabetes than those naturally conceived (aOR 7.86, 95% CI 1.55-39.87). No differences were found regarding neonatal outcomes between groups. Conclusions: Compared with naturally conceived MCDA twin pregnancies, those conceived through ART displayed a significantly higher risk of developing gestational diabetes. No differences regarding other pregnancy complications, mode of delivery, or neonatal outcomes were found between groups.

Perinatal Outcome of Singletons Born after Using a Simplified Low-Cost IVF Culture System and All Singletons Born in Flanders (Belgium) between 2012 and 2020.

BACKGROUND: We developed a simplified IVF culture system (SCS) which has proven to be effective and safe in a selected IVF cohort. METHODS: Preterm birth (PTB) and low birth weight (LBW) of 175 singletons born after using the SCS, 104 after fresh embryo transfer (ET), and 71 after frozen embryo transfer, were compared with all singletons born in Flanders between 2012 and 2020 conceived after natural conception, ovarian stimulation (OS), and assisted reproduction (IVF/ICSI). FINDINGS: The proportion of preterm (<37 weeks) births was significantly higher in the case of IVF or ICSI, followed by hormonal treatment, compared to spontaneous pregnancies. There was no significant difference in PTB between SCS and any of the other groups. Concerning the average birth weight we found no significant difference between singletons born after natural conception and SCS. However, a significant difference in average birth weight was found between SCS singletons and singletons born after IVF, ICSI and hormonal treatment, with a significantly higher birth weight in the SCS group. This difference was also observed in the proportion of babies weighing less than 2500 g, with significantly more LBW babies in the IVF and ICSI group compared to the SCS newborns. INTERPRETATION: Taking into account the small series, PTB and LBW rates in SCS singletons were found to be comparable with singletons born after natural conception. Compared to babies born after ovarian stimulation and IVF/ICSI, SCS singletons had a lower PTB and LBW rates, although the differences were not significant for PTB. Our results confirm previous reports on reassuring perinatal outcomes after using the SCS technology.

The cost-effectiveness of using a prognosis-tailored strategy model to triage couples with idiopathic infertility for assisted reproduction technology.

OBJECTIVES: To evaluate whether a prognosis-tailored triage of ART for couples with idiopathic infertility by using the Hunault prognostic model can decrease the cost of treatment without compromising the chance of live birth. STUDY DESIGN: This is a retrospective study conducted in an Australian fertility clinic. Couples seeking infertility consultation who were subsequently found to have idiopathic infertility after evaluation were included. We compared the costs per conception leading to live birth of the prognosis-tailored strategy with the immediate ART strategy, which generally reflects the current practice in Australian fertility clinics, over a 24-month period. In the prognosis-tailored strategy, for each couple, the prognosis for natural conception was assessed using the well-established Hunault model. Total cost of treatments were calculated as the sum of typical out-of-pocket and Australian Medicare cost (Australian national insurance scheme). RESULTS: We studied 261 couples. In the prognosis-tailored strategy, the total cost was $2,766,781 and the live birth rate was 63.9%. In contrast, the immediate ART strategy yielded a live birth rate of 64.4% with a total cost of $3,176,845. Implementing the prognosis-tailored strategy using the Hunault model saved $410,064 in total and $1,571 per couple. The incremental cost-effectiveness ratio (ICER) was $341,720 per live birth. CONCLUSION: In couples with idiopathic infertility, assessment of prognosis for natural conception using the Hunault model and delaying ART for 12 months in couples with favourable prognoses can considerably reduce costs without significantly compromising live birth rates.

Anthropometric measurements of term singletons at 6 years of age born from fresh and frozen embryo transfer: A multicenter prospective study in Japan.

Purpose: The purpose of this study is to compare anthropometric measurements between term singletons conceived via fresh embryo transfer (FreET) and frozen embryo transfer (FET) and those born via natural conception (NC) or fertility treatments milder than assisted reproductive technology (non-ART) at 6 years of age. Methods: A total of 8149 children were enrolled, and questionnaires about anthropometric measures (weight, height, BMI) were addressed to parents, when the children were 1.5, 3, and 6 years of age. A total of 3299 term singletons were enrolled at birth: 533, 476, 916, and 1374 in the NC, non-ART, FreET, and FET groups, respectively. Results: A total of 1635 term singletons (290, 176, 467, and 702 in the NC, non-ART, FreET, and FET groups respectively) were enrolled until 6 years of age (follow-up rate, approximately 50%). When non-ART group was used as control, the FreET children were 1.0 cm taller than the non-ART children at 6 years of age, after adjusting for confounding factors. However, no differences were observed in the anthropometric data among the non-ART, ART, and NC children at 6 years of age. Conclusion: At 6 years of age, term singletons were taller in the FreET group than in the non-ART group, after adjusting for confounders.

A Cohort Study Comparing the Growth and Neurodevelopmental Outcome of Babies Conceived by Assisted Reproductive Technology with Those of Naturally Conceived Babies from Birth till 24 Months.

OBJECTIVE: To compare the growth and neurodevelopmental outcome of term, singleton babies conceived by assisted reproduction with those of naturally conceived babies. METHODS: A cohort study evaluating the growth delay in terms of proportion of babies with wasting (W/L < -2SD) at 6, 12 and 24 mo follow-up. Developmental delay was defined as either motor or mental developmental quotient < 70 in DASII. RESULTS: Amongst the 128 artificially conceived babies, at 6 and 12 mo, the proportions of babies with wasting (21.1% and 17.2%), motor (7.03%, 6.3%), and mental developmental delays (5.5% and 3.9%) were significantly higher (p < 0.05) compared to the naturally conceived babies (10.94%, 8.6%, 1.6%, 0.8%, 0.8% and 0%, respectively). However, at 24 mo, the difference in outcomes were not statistically significant (p > 0.05). CONCLUSION: The growth and neurodevelopment of artificially conceived babies may be delayed in early infancy but they normalize to catch up with their naturally conceived peers by 24 mo.

Neurodevelopmental Outcomes of Pregnancies Resulting from Assisted Reproduction: A Review of the Literature.

The term infertility is defined as the lack of conception within 1 year of unprotected intercourse. It affects more than 80 million individuals worldwide. It is estimated that 10-15% of couples of reproductive age are challenged by reproductive issues. Assisted reproduction techniques (ART) are responsible for more than 4% of live births. Our aim is to review the research on neurodevelopmental outcomes of newborns born after the implementation of assisted reproduction methods compared to those conceived naturally. We conducted a comprehensive search of the PubMed, Crossref and Google Scholar electronic databases for related articles up to June 2022 using the PRISMA guidelines. Our research revealed a large number of long term follow-up studies between 2 and 18 years of age, with comparable developmental outcomes. Many studies compared the effects of different infertility treatments against natural conception. The review of the literature revealed that ART is safe, as the majority of studies showed no effect on the neurodevelopmental outcomes of the offspring. In most cases when such an effect was observed, it could be attributed to confounding factors such as subfertility, multiple pregnancies and gestational age at delivery. Finally, the increase in the prevalence of neurodevelopmental disorders after ART, as described in studies with statistically significant results, is predominantly marginal, and given the low incidence of neurodevelopmental disorders in the general population, its clinical significance is debatable.

A Multidisciplinary Quality of Care Path For Couple Infertility: Development of An Integrated Approach Founded on A Multidisciplinary, Personalistic, and Ecological Model For Couple Fertility.

The Path of Fertile Family (FFP) is a service for couples experiencing infertility, aimed to obtain natural conception, as an alternative to assisted reproductive techniques, developed in 2018 and provided by the Counseling Centre of Centro della Famiglia Foundation, an institute of culture and pastoral care of the Diocese of Treviso, in cooperation with the local socio-health unit. FFP offers to infertile couples a specific multidisciplinary path of care, including the involvement of specific gynecological, andrological, endocrinological, and psycho-relational competences, together with fertility awareness. It represents an "experiential laboratory" for the multidisciplinary diagnosis and treatment of infertility, for understanding relational processes, for the development of operational strategies and above all for the verification of the goodness of a lifestyle that is able to harmonize the couple's project and the family's project, couple satisfaction and parental openness. The setting of the service draws inspiration and reference from three paradigms from which significant ethical choices derive: the ecological perspective of fertility, the relational intimacy of the couple and a multidisciplinary approach. From the three founding paradigms, FFP model has been developed and progressively implemented in order to define a specific FFP Quality of Care Path (QCP) for couple infertility. Although further studies are needed to better clarify the role of each studied variable in a complex monitoring system, we identified for the first time a QCP Path based on 7 variables we present here two illustrative cases: the first one in which a natural conception has been obtained and the second one, in which the focus has been moved from natural conception to the reconstruction of relational competence. Further studies will demonstrate, on large scale, the efficacy of our protocol and of the analyzed variables. Summary: This paper provides an overview of the conceptual and methodological process of implementing the monitoring of the path of infertile couples towards natural conception in harmony with their relational life project. A multi-professional team accompanies couples in overcoming the obstacles to fertility and in the progressive awareness that parenting is not only biological. The result is a range of goals to strive for. The reference paradigms of the service justify the ethical choices of the couple and the team. The operating protocol supports the couple commitment and guides professionals in their effective action if competent and concerted. The variables identified are the monitoring tool that gradually indicates the degree of the path progress.

The de novo aberration rate of prenatal karyotype was comparable between 1496 fetuses conceived via IVF/ICSI and 1396 fetuses from natural conception.

PURPOSE: To evaluate the cytogenetic risk of assisted reproductive technology (ART) by comparing the incidence of de novo chromosomal abnormalities between fetuses conceived via in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and natural conception. MATERIALS AND METHODS: Prenatal invasive diagnostic testing (amniocentesis and cytogenetic analysis) was performed on 1496 fetuses conceived via IVF/ICSI (IVF/ICSI group) and 1396 fetuses from natural conception (NC group). The incidence of de novo chromosomal abnormalities (including aneuploidy and chromosomal structure abnormalities) was used to evaluate the cytogenetic risk of ART. For statistical analysis, χ2-test was used for binary dependent variable. The significance level was P < 0.05 and confidence interval was 95%. RESULT(S): The IVF/ICSI group displayed a modest increase in the overall de novo chromosomal abnormality rate compared with that in the NC group but with no statistical significance (6.75% vs. 6.16%; χ2 = 0.42, P > 0.05). The incidence of abnormal karyotypes was also not significantly different between the IVF/ICSI and NC groups in different maternal ages, including ≥ 35 years group (7.55% vs. 9.60%, χ2 = 1.40, P > 0.05) and < 35 years group (6.20% vs. 4.54%, χ2 = 2.51, P > 0.05). Moreover, there was no difference in the proportion of aneuploid and structural abnormalities in detected karyotypes between the IVF/ICSI and NC groups. Logistic regression analysis showed no significant association between the method of pregnancy and de novo chromosomal abnormalities (odds ratio (OR) 1.03; 95% CI 0.71-1.50; P = 0.86) after adjusting for other confounding factors. CONCLUSION(S): Fetuses conceived via IVF/ICSI had a slight but not statistically significant increase in de novo abnormal karyotypes compared to those in naturally conceived fetuses. Our findings indicate no significant association between de novo fetal chromosomal abnormalities and the pregnancy method in high-risk pregnancies in the second trimester. For these pregnancies with a high risk but with a normal karyotype, further genetic testing is required for diagnosis.

The predictive value of anti-Müllerian hormone for natural conception leading to live birth in subfertile couples.

RESEARCH QUESTION: What is the predictive value of serum anti-Müllerian hormone (AMH) level for natural conception and its clinical effect on subfertile couples? DESIGN: A retrospective cohort of ovulatory women seeking fertility consultation in a private fertility clinic. Couples who had an immediate indication for IVF were excluded. All natural conceptions leading to live birth before the start of assisted reproductive technology were followed within 12 months of the initial consultation. A prediction model was developed by updating the Hunault model with serum AMH to predict the probabilities of achieving a natural conception leading to live birth. RESULTS: A total of 325 couples were included in the final analysis. The estimated cumulative proability of achieving natural conception leading to live birth within 12 months was 20.9% (95% CI 12.9% to 28.2%). The categorical net reclassification improvement of AMH is 7.6%. For couples with a predicted chance of natural conception changed from poor (<30%) by the reference model to good (≥30%) by the updated model, the cumulative natural conception rate leading to live birth was 52.0%. For couples who had predicted chance of natural conception changed from good to poor by the updated model, the rate was 18.9%. CONCLUSIONS: The addition of serum AMH to the routine fertility work-up may improve prognosis-based treatment policy and help to prevent unnecessary costs and stress for couples. Prospective validation of the updated model with AMH is required before clinical application.

Pre-eclampsia in pregnancies resulting from oocyte donation, natural conception or IVF: a systematic review and meta-analysis.

STUDY QUESTION: What is the prevalence of pre-eclampsia (PE) in pregnancies after oocyte donation (OD) compared to natural conception (NC) and to IVF with autologous oocytes (AO)? SUMMARY ANSWER: Overall the prevalence of PE after OD was 4-5 times higher than after NC and 2-3 times higher than after IVF with AO. WHAT IS KNOWN ALREADY: The indication for OD is expanding to lesbian women requesting shared lesbian motherhood. Previous reviews have shown that the risk of PE is higher in pregnancies after OD than after NC and after IVF with AO. Classification on the severity of PE is lacking as is the relationship with known risk factors such as maternal age and multiple gestations. Furthermore the actual prevalence of PE in pregnancies resulting from OD is not known. STUDY DESIGN, SIZE, DURATION: A systematic review and meta-analysis was conducted. A literature search was performed using the following databases: PubMed, EMBASE and CINAHL, OpenGrey and Greynet from January 1980 through July 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included retrospective and prospective cohort studies. The study population consisted of pregnancies after OD and NC or IVF and data had to be available about prevalence of PE. We compared the risk of (severe) PE in OD versus NC and IVF pregnancies, subgrouped by plurality and maternal age. We calculated individual and pooled odds ratios (OR) and prevalence estimates with 95% CI using a random effect model, while heterogeneity was assessed by the I2. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 27 studies comprising of 7089 OD pregnancies, 1 139 540 NC pregnancies and 72 742 IVF pregnancies were available for analysis. The risks of PE and severe PE was increased in OD pregnancies compared to NC pregnancies (pooled OR of all subgroups: 5.09, 95% CI: 4.29-6.04; I2 = 19% and OR: 7.42, 95% CI: 4.64-11.88; I2 = 49%, respectively). This suggests that compared to a PE risk of 2.9% with NC, the risk with OD was between 11.5% and 15.4%. Compared to a severe PE risk of 0.5% with NC, the risk with OD was between 2.3% and 5.6%. The pooled adjusted OR for PE was 3.24 (95% 2.74-3.83) for OD versus NC pregnancies. The risks of PE and severe PE were also increased in OD pregnancies compared to IVF pregnancies (pooled OR of all subgroups: 2.97, 95% CI: 2.49-3.53; I2 = 51% and OR: 2.97, 95% CI: 2.15-4.11; I2 = 0%, respectively). This suggests that compared to a PE risk of 5.9% with IVF, the risk with OD was between 13.5% and 18.0%. Compared to a severe PE risk of 3.3% with IVF, the risk with OD was between 6.8% and 12.2%. The pooled adjusted OR for PE was 2.67 (95% 2.28-3.13) for OD versus IVF. The pooled prevalence of PE in singleton pregnancies after OD was 10.7% (95% CI 6.6-15.5) compared to 2.0% (95% CI 1.0-3.1) after NC and 4.1% (95% CI 2.7-5.6) after IVF. The prevalence in multiple pregnancies was 27.8% (95% CI 23.6-32.2) after OD, 7.5% (95% CI 7.2-7.8) after NC and 9.7% (95% CI 6.2-13.9) after IVF. LIMITATIONS, REASONS FOR CAUTION: The precise definition of PE is still a matter of debate. The different criteria could have affected the prevalence estimate. WIDER IMPLICATIONS OF THE FINDINGS: Nearly one in six women will suffer PE after OD. Although it is uncertain whether these risks are consistent for lesbian couples undergoing shared motherhood, we feel that women who can conceive naturally could be advised to reconsider. In women with primary ovarian insufficiency, we feel that factors that may increase risk of PE ever further, such as double embryo transfer, should be avoided whenever possible. STUDY FUNDING/COMPETING INTEREST(S): No funding or competing interests. REGISTRATION NUMBER: CRD42020166899.

Expectant Management Before In vitro Fertilization in Women Aged 39 or Above and Unexplained Infertility Does Not Decrease Live Birth Rates Compared to Immediate Treatment.

Unexplained infertile couples can have further expectant management before starting assisted reproductive treatments. However, ovarian reserve and in vitro fertilization (IVF) outcomes rapidly decline after 39 years or more. It is thus important to clarify whether a waiting policy is also appropriate for women of advanced age. Couples who had access to a waiting list for approximately 1 year before receiving reimbursed public IVF were compared with those paying for access to immediate treatment. To allow for comparisons between these two strategies, we followed up couples who opted to pay for 1 year after the last embryo transfer from their first cycle. We calculated the proportion of live births in both groups and compared these using logistic regression models and a two-sample Z test for equality of proportions. Six hundred thirty-five couples were evaluated. Out of 359 couples in the immediate group, 70 (19.5%) had a live birth of which 11 after natural conception and 59 after IVF. Out of 276 couples in the waiting group, 57 (20.7%) had a live birth of which 37 after natural conception and 20 after IVF. There was no statistically significant difference between the two strategies in terms of the crude cumulative live birth rate (cLBR). The adjusted odds ratio of 0.69 (95%CI:0.39-1.22) did not change this conclusion as our sensitivity analyses. The cLBR for the 'waiting before IVF' and the 'immediate' strategies were similar. Further studies are needed to better characterize couples affected by unexplained infertility in order to individualize treatment strategies.

The Kind of Conception Affects the Kind of Cesarean Delivery in Primiparous Women.

BACKGROUND: So far, multiple factors have been found to be related to the IVF procedure, the most prevalent being extremes of maternal age, infections, previous gynecological history, infertility and others. Although women achieve the coveted pregnancy with the development of IVF technology, the rapid increase contributes to the increase of primary cesarean sections rates. OBJECTIVE: The aim of the study was to identify if the kind of conception affects the kind of cesarean delivery among primiparous women in Greece. METHODS: This cross-sectional observational study took place from September 2019 to February 2020 at the University Hospital of Larisa in Greece. One hundred and sixty-two primiparous women who underwent a cesarean section (c-section) after IVF (n=27) and natural conception (n=135) participated in the study. RESULTS: The mean age of the IVF and natural conception groups were 36.22 and 31.08 years, respectively. Nineteen (70.4%) women of the IVF group had a previous medical or gynecological history in contrast to 48 (35.6%) women of the natural conception group. Only 55.6% of the IVF group had a full-term pregnancy unlike 88.1% of women in the natural conception group. An elective c-section was performed in 18 (66.7%) of the women who conceived after IVF, as opposed to 45 (33.3%) of the women who conceived naturally. CONCLUSION: This cross-sectional study showed that IVF conception was associated with high rates of elective cesarean section as opposed to women with natural conception. The causes of c-sections must be evidence based because the primary cesarean delivery is a major factor contributing to increased c-section rates.