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Please cite this paper as: Salomon L, Hourrier S, Fanchin R, Ville Y, Rozenberg P. Is first-trimester crown-rump length associated with birthweight? BJOG 2011; DOI: 10.1111/j.1471-0528.2011.03009.x. Objective To evaluate the relationship between first-trimester crown-rump length (CRL) and birthweight (BW) Z scores. Design Retrospective cohort study. Setting Two tertiary centres in France. Population Three hundred and seventeen pregnancies conceived through assisted reproductive techniques between April 2001 and December 2008. Methods We used CRL and worked forward to BW. Only pregnancies examined during the first trimester by an Fetal Medicine Foundation-certified operator were included. CRL was expressed as Z scores, and BW was transformed into Z scores by taking gestational age and gender into account. The influence of abnormal first-trimester CRL Z scores on BW was examined. Main outcome measures Weight and gestational age at birth. Results Birth weight was significantly greater in babies with larger CRL: BW Z scores (±SD) were −0.36 (±1.05), −0.27 (±0.97), −0.10 (±1.04) and 0.13 (±0.96) in the first, second, third and fourth quartiles of CRL Z scores, respectively ( P = 0.01). In contrast, there was no difference in gestational length according to the quartiles of the CRL Z scores. The CRL Z score was a significant predictor of the BW Z score ( β = 0.17, P = 0.001). After adjustment for maternal body mass index, a one-point increase in the first-trimester CRL Z score (i.e. 3.6 mm) was associated with a 39% decrease, 64% increase, 114% increase and 62% increase in the risk of having a BW below the 10th centile [odds ratio (OR), 0.61; 95% confidence intervals (95% CI), 0.39; 0.95; P = 0.03], above the 90th centile (OR, 1.64; 95% CI, 1.03; 2.60; P = 0.02), above the 95th centile (OR, 2.14; 95% CI, 1.25; 3.68; P = 0.006) and above 4000 g (OR, 1.62; 95% CI, 1.04; 2.51; P = 0.04), respectively. Conclusions Variations in BW may be partly explained by differences in growth trajectories that may express as early as the first trimester. [ABSTRACT FROM AUTHOR]

In-vitro maturation of oocytes (IVMI is a new IVF technology developed in order to avoid iatrogenic complications of standard IVF treatments. This technique is particularly useful in patients suffering from polycystic ovary syndrome (PCOS) who are concerned with the risk of ovarian hyperstimulation syndrome. This technique is nowadays routinely practised in many international centres. However, the efficiency of this technique needs to be improved for a better support of maturation conditions to maximize oocyte developmental competence. In order to improve IVM results, the efficiency of two 1VM media was retrospectively compared. Ninety-three PCOS candidates undergoing their first IVM cycle were included in this study, and IVM was conducted with TCM-199 or IVM-Medicult medium. This is the first study comparing two maturation media. Both media resulted in the same results concerning total oocyte maturation, fertilization, early embryo development and pregnancy rates. [ABSTRACT FROM AUTHOR]

Investigates the feasibility of using clomiphene citrate in combination with gonadotrophins, in a luteinizing hormone-releasing hormone (LHRH) antagonist protocol. Role of LHRH antagonist in assisted reproductive technique; Materials and methods used in the study; Results.

An abstract of the conference paper "Relationship between first trimester growth and birth weight at term" by S. Hourrier and colleagues is presented.

Study Question: Are in vitro maturation (IVM) rates of cumulus-oocyte complexes (COCs), retrieved from breast cancer patients seeking urgent fertility preservation (FP) before neoadjuvant chemotherapy, different between those recovered in the follicular or in the luteal phase of the cycle?Summary Answer: The present investigation reveals no major difference in the number of COCs recovered or their IVM rates whatever the phase of the cycle at which egg retrieval is performed, suggesting that IVM is a promising tool for breast cancer patients seeking urgent oocyte cryopreservation.What Is Known Already: FP now represents a standard of care for young cancer patients having to undergo gonadotoxic treatment. Mature oocyte cryopreservation after IVM of COCs has been proposed for urgent FP, especially in women, who have no time to undergo ovarian stimulation, or when it is contraindicated.Study Design, Size, Duration: From January 2011 to December 2014, we prospectively studied 248 breast cancer patients awaiting neoadjuvant chemotherapy, aged 18-40 years, candidates for oocyte vitrification following IVM, either at the follicular or the luteal phase of the cycle.Participants/materials, Setting, Methods: Serum anti-Müllerian hormone and progesterone levels and antral follicle count (AFC) were measured prior to oocyte retrieval. Patients were sorted into two groups according to the phase of the cycle during which eggs were harvested (Follicular phase group, n = 127 and Luteal phase group, n = 121). Number of COCs recovered, maturation rates after 48 h of culture and total number of oocytes cryopreserved were assessed. Moreover, the oocyte retrieval rate (ORR) was calculated by the number of COCs recovered ×100/AFC.Main Results and the Role Of Chance: In the Follicular and the Luteal phase groups, women were comparable in terms of age, BMI and markers of follicular ovarian status. There was no significant difference in the number of COCs recovered (mean ± SEM), 9.3 ± 0.7 versus 11.1 ± 0.8, and ORR (median (range)) 43.1 (1-100) versus 47.8 (7.7-100)%. Moreover, maturation rates after 48 h of culture (median (range)) were comparable in the follicular and luteal phase groups, 66.7 (20-100) versus 64.5 (0-100)%. Finally, the total number of oocytes cryopreserved (mean ± SEM) was similar in both groups (6.2 ± 0.4 versus 6.8 ± 0.5).Limitations, Reasons For Caution: Despite the intact meiotic competence of immature oocytes recovered during the follicular or the luteal phase, there is a dramatic lack of data regarding the outcome of IVM oocytes cryopreserved in cancer patients.Wider Implications Of the Findings: IVM of oocytes may be an interesting method of FP in urgent situations. Improving the culture conditions will be needed to increase the maturation rates and the overall potential of in vitro matured oocytes.Study Funding/competing Interests: None.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

A response by L. J. Salomon and colleagues to a letter to the editor regarding their article "Is first-trimester crown-rump length associated with birthweight?" in the 2011 issue is presented.

Background: Since in rodents anti-Müllerian hormone (AMH) has been shown to inhibit antral follicle responsiveness to FSH, we aimed at verifying whether a relationship exists between serum AMH levels and antral follicle responsiveness to exogenous FSH in normo-cycling women. Methods: Serum AMH, estradiol (E(2)) and FSH levels were prospectively measured on cycle day 3 in patients undergoing controlled ovarian hyperstimulation (COH) with a time-release GnRH agonist and standardized FSH doses. In 162 patients, follicles were counted after pituitary suppression and before FSH administration (baseline; small antral follicles; 3-8 mm), and on the day of hCG (dhCG; pre-ovulatory follicles; 16-22 mm). Antral follicle responsiveness to FSH was estimated by the Follicular Output RaTe (FORT), determined by the ratio pre-ovulatory follicle count on dhCG × 100/small antral follicle count at baseline. Results: Serum AMH levels were positively correlated with the number of small antral follicles at baseline (r = 0.59; P < 0.0001) and pre-ovulatory follicles on dhCG (r = 0.17; P < 0.04). Overall, FORT was 47.5 ± 1.4% and failed to be influenced by the woman's age, BMI or basal E(2) and FSH level. Conversely, multiple regression analysis showed that FORT was negatively correlated with AMH levels (r = -0.30; P < 0.001), irrespective of duration of COH and total FSH dose. Conclusions: The percentage of follicles that effectively respond to FSH by reaching pre-ovulatory maturation is negatively and independently related to serum AMH levels. Although the mechanisms underlying this finding remain unclear, it is in keeping with the hypothesis that AMH inhibits follicle sensitivity to FSH. [ABSTRACT FROM AUTHOR]

All indicates that anti-Müllerian hormone (AMH), though initially studied for its importance on male development, plays an inhibiting role on the initial and cyclic processes of follicular recruitment. The aspects involved in its regulation are still poorly understood, but the oocyte, some steroids, and follicular development itself seem to be involved. In addition, AMH has become an important clinical marker of ovarian functioning for many reasons, including its exclusive production by granulosa follicles at many stages of development, its probable FSH independence, its low inter and intracycle variability and its reliable quantitative (qualitative?) relationship with ovarian follicles and their response to exogenous FSH. The growing interest in ovarian AMH incited us to review some important fundamental and clinical publications in this field. [Copyright &y& Elsevier]

The accurate assessment of ovarian reserve is an essential step before the treatment of infertile couples. Ovarian reserve could either be evaluated through clinical or biological parameters, but ultrasound plays a remarkable role, since it permits the direct visualization and count of ovarian antral follicles. Nevertheless, the available literature data are conflicting about the real sensibility and specificity of this method to predict the exact number of retrieved oocytes or the occurrence of pregnancy after a procedure for medical assisted reproduction. New technologies have been developed, as the 3D-ultrasound, who does not ameliorate ultrasound accuracy, but permits the reduction of the time necessary for patient's examination and virtually eliminates inter- and intra-observer bias. The place of the ovarian artery flow evaluation by Doppler remains unclear and need more studies. [Copyright &y& Elsevier]

Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common hereditary renal cystic diseases, and is caused by mutations in the PKHDI gene. Due to the poor prognosis, there is a strong demand for prenatal diagnosis. Preimplantation genetic diagnosis (PGD) represents an alternative because it avoids the physical and emotional trauma of a pregnancy termination in the case of an affected fetus. A standardized single-cell diagnostic procedure was developed, based on haplotype analysis, enabling PGD to be offered to couples at risk of transmitting ARPKD. Six linked markers within (D6S 1714 and D6S243), or in close proximity to (D6S272, D6S436, KIAA0057, D6S1662) the PKHDI gene were tested by multiplex nested-polymerase chain reaction (PCR), using a Qiagen multiplex PCR kit. PCR analyses were carried out on 50 single lymphocytes. The amplification rate was excellent (100%), with an allele drop-out (ADO) rate ranging from 0 to 8%. Five PGD cycles were performed and 23 embryos were biopsied and analysed using this test. Transferable embryos were obtained in 4 cycles, resulting in two pregnancies and the birth of a healthy boy. This standardized diagnostic procedure allowed the detection of recombination, contamination, and ADO events, providing high assay accuracy with wide applicability. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: This article deals with the place of adoption for couples involved in a medical help for procreation. The question is: do these couples wait for their gynaecologist''s advice before beginning a procedure of adoption or do they launch such a procedure before? Patients and methods: We have questioned 90 couples, on the first day of their treatment in our unity, about the place of adoption in their desire for a child. Are they in favour or against adoption? Have they already begun or not to think, to read, to make a decision about adoption? Results: In this research, 49% of theses couples are not in favour of adoption, especially when they have already had children through medical help. 84,5% thought about adoption as soon as they received the announcement of the infertility. 69% have shown their interest in adoption by reading books, watching TV or by speaking with adoptive parents or adopted children. 29% have begun a procedure of adoption but only 18% really intend to adopt a child. Discussion and conclusion: Most of the infertile couples do not wait for their clinician''s advice to be interested in adoption. But they probably have to hear from their clinician that the treatments are definitively finished to become completely involved in the adoption process. Some of them will prefer to stay even so without children or to think about the gamete''s donation. [Copyright &y& Elsevier]

Since the first preimplantation diagnosis (PGD) procedure in 1990, indications have regularly increased. The follow up of children born after PGD show no adverse outcomes but no studies have been reported concerning the pregnancy and possible complications related to PGD procedure. This retrospective study aimed at comparing obstetrical and neonatal outcomes in 87 singleton pregnancies obtained after ICSI/PGD versus 115 singleton pregnancies obtained after ICSI. Patients characteristics were not significantly different excepted for gestity and parity which were higher in the PGD group. The rates of maternal hospitalisation, premature labour, and gestational diabetes were significantly higher in the ICSI group (23.3% versus 12.8%, 13.9% versus 4.6% et 10.4% versus 1.2%, p < 0.005 respectively). Patients of PGD group had higher rates of first trimester bleeding, praevia placenta, and preeclampsia without reaching the statistical significance. Birth weights, term delivery, and delivery modalities were similar in both groups. Pregnancies obtained after ICSI/PGD procedures don't seem to be considered as high risk pregnancies as compared to ICSI pregnancies. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA) diseases are serious disorders with maternal inheritance. Because there is no efficient therapy in these disorders, couple at risk to transmit mtDNA mutations often request for prenatal (PND) or preimplantation (PGD) diagnosis. These practices mainly relied on the quantification of heteroplasmy level in fetal tissue (DPN) or blastomere (PGD), based on postnatal observations showing a correlation between the mutant load and the risk of developing severe symptoms. Preconceptional diagnosis, performed before fertilization, might be an ethically preferable way to perform a diagnosis since it avoids the potential discarding of embryos. However, it requires that the mtDNA mutant load assessed on polar body be an accurate indication of the mutant load in the corresponding oocyte/embryo. Heteroplasmy was assessed in 48 first polar bodies (PBI) and corresponding ovocytes/embryos from 3 patients at risk of transmitting (i) MELAS syndrome by mutation m.3243A>Gi n the tRNALeu gene (n = 27), (ii) MERRF syndrome by mutation m.8344A>G in the tRNALys gene (n = 15) and (iii) Leigh syndrome by the mutation m.9185T>G located in the ATPase6 gene (n = 6). The results showed that (i) the absence of mutation in PBI (n = 5) was correlated with the absence of mutation in the corresponding oocyte or embryo; (ii) when PBI were heteroplasmic (n = 43), significant differences were found between PBI and counterpart heteroplasmy levels. Overall, heteroplasmy rates were higher in PBI than in counterparts, with mutant load differentials ranging from -34 to +34%. By fixing the cutoff points below which embryos are considered eligible for transfer at 30%, restricting the analysis to PBI would have lead to transfer 4 embryos carrying mutant loads over 40%, and not to transfer 5 embryos carrying less than 30% of mutation. These differences, which were not observed in heteroplasmic mouse models, support the need to achieve more data on mtDNA segregation in humans. They will preclude PGD for mtDNA mutations based on PBI analysis, unless the purpose is the transfer of "mutation-free" embryos only. [ABSTRACT FROM AUTHOR]

A correction to the article "Successful preimplantation genetic diagnosis for autosomal recessive polycystic kidney disease by haplotype analysis" is presented.

Objective: The aim of the present study was to evaluate clinical and embryo parameters to predict embryo ploidy., Methods: In this retrospective analysis, we studied 838 biopsied day-5 blastocysts from 219 patients in the period from May 2021 to July 2022. All embryos were morphologically classified before biopsy and were divided into two groups according to genetic test results. Euploid embryos (299) were compared with aneuploid embryos (539) based on maternal age, anti-Mullerian hormone, antral follicle count, and embryo morphology., Results: Maternal age (36.2±3.0) of euploid embryos was lower than maternal age (37.1±2.5) of aneuploid embryos (p<0.0001). AMH levels were higher (3.9±1.2) in the group of euploid embryos than in the group of aneuploid embryos (3.6±1.3, p<0.0001). However, the AFC was not different in the group of euploid embryos (15.3±6.0) compared to the group of aneuploid embryos (14.5±5.9, p=0.07). The presence of aneuploidy was negatively correlated with top embryo quality (embryos 4AA and 4AB). All euploid embryos (299) were top quality versus 331 of 539 (61.49%) aneuploid embryos (p<0.0001)., Conclusions: We found that euploid embryos were associated with lower maternal age, higher AMH levels, and higher quality embryos.

Objective: To assess the association between serum level of progesterone during stimulation and in the luteal phase with pregnancy rate in a cohort of patients undergoing in vitro fertilization and embryo transfer (IVF-ET) on day 5., Methods: Retrospective Cohort Study. Patients: 62 infertile women, aged 24-42 years, undergoing ART at our center from May 2019 to May 2021. Progesterone was evaluated during ovarian stimulation on Day 2, Day 6, and Day 8 of stimulation, day of trigger (P4dhCG), and on the day of blastocyst transfer with 5 days of progesterone supplementation (P4d5+). We also calculated the difference of P4d5+ with P4dhCG. (∆P4). Then we divided the patients into two groups based on progesterone serum levels at P4d5+; <10ng/ml (Group A), ≥10ng/ml (Group B). The Student's t-test was performed for continuous variables; Mann-Whitney's Test and Spearman's Test were used where appropriate for categorical variables. p<0.05 was considered statistically significant., Results: There were positive correlations between βhCG positive with P4d5+ (p<0.001; Rho 0.770) and ∆P4 (p<0.001; Rho 0.703). The pregnancy rate doubled when the serum progesterone level was ≥10ng/ml on the fifth day of progesterone supplementation compared with P4<10ng/ml (44% vs. 21%, respectively)., Conclusions: The pregnancy rate was positively correlated with the serum P4 level on the fifth day of progesterone supplementation and with the difference between the serum progesterone level in the Dd5+ / dhCG. A higher pregnancy rate was observed when serum progesterone level on the fifth day of progesterone supplementation was ≥10ng/ml.

Purpose: To identify the FSH receptor (FSHR) variant and efficacy of in vitro maturation (IVM) in a 28-year-old woman with secondary amenorrhea, primary infertility, and ovarian resistance to FSH, and to analyze the genotype-to-phenotype relationship in cases of FSHR mutation for the development of an IVM algorithm for use in patients with gonadotropin resistance syndrome (GRS)., Methods: Oocytes retrieved after menstruation induction with norethisterone, followed by daily estrogen and an ovulatory trigger, underwent IVM, ICSI, and culture in a time-lapse (TL) incubator. Embryo transfers were performed on day 2, and after thawing on day 5. Genes associated with disorders of sex development were sequenced for both the patient and her parents. All reported cases of FSHR mutation were analyzed to investigate genotype/phenotypic relationships., Results: After ovum pickup, seven of 16 oocytes matured and all fertilized. After unsuccessful day 2 transfer, our patient delivered with a thawed day 5 blastocyst, the sole embryo without abnormal TL phenotypes. Genetic analysis revealed a new composite heterozygous FSHR variant. Analysis of our patient case with published cases of GRS revealed associations among FSHR variant genotype, location on the FSHR, functionality of tested variants, and type of amenorrhea. An algorithm for application of IVM for GRS patients was developed., Conclusions: We report two novel variants of the FSHR. Although IVM successfully matured some oocytes, only one resulted in an embryo with normal TL phenotypes. We recommend FSHR genetic testing in GRS patients, which will help guide their suitability for IVM.

Objective: The aim of the present prospective study was to evaluate which ovarian reserve marker would be more reliable as the quality of the A + B embryos (day 3 and blastocyst)., Methods: We ran a prospective study with 124 infertile women, aged 24-48 years, from 2017 to 2018. The patients were divided into 3 groups according to age and the subgroups were compared for AMH, AFC, number of A+B embryos. New division of the 3 groups was performed based on the AMH, and the subgroups were compared for age, AFC and number of A+B embryos. Finally, we divided the patients into 3 groups, based on the AFC, and we compared the subgroups for age, AMH and number of A+B embryos. P<0.05 was considered statistically significant., Results: When the 124 patients were divided according to age, we found a significant fall in an A+B embryo quality (day3; blastocyst) after 35 years (p<0.038; p<0.035), and more severely after 37 years (p<0.032; p<0.027). When the 124 patients were divided according to AMH, there was a significant fall in A+B embryo quality (day 3; blastocyst), with AMH<1ng/ml (p<0.023; p<0.021). When the 124 patients were divided according to AFC, there was a significant fall in A+B embryo quality (day 3; blastocyst) with AFC<7 (p<0.025; p<0.023). These markers had significant associations with embryo quality (p<0.005)., Conclusion: Age, AFC and AMH have significant associations with A +B embryo quality on day 3 and blastocyst.

Objective: To evaluate the effects of three different estrogen used for endometrium preparation on pregnancy rate, as well as hormone profile on day 5 frozen embryo transfer (FET) cycles., Methods: Retrospective, observational study. Setting: A tertiary teaching and research private reproductive medicine center. Patients: Ninety patients who were undergoing endometrium preparation for day five frozen embryo transfer cycle (FET). Intervention(s): The women were divided in three groups according to the administration route of estrogen (E2): oral (Primogyna), transdermal patches (Estradot), or transdermal gel (Oestrogel Pump). These administration routines of estrogen are equivalent to 6mg of estradiol daily. All women received 600mg of vaginal progesterone (P) per day (Utrogestan) for luteal phase support. We drew blood samples on starting P day, as well as on beta hCG day for E2 and P measurements. Main Outcome Measure(s): Clinical pregnancy rates (PR)., Results: Patient features in the three groups were comparable. There were no significant differences concerning implantation rate, clinical PR, miscarriage rate, multiple-pregnancy rate, or E2 and P levels on starting P day and on beta hCG day., Conclusions: In FET cycles with oral (Primogyna) or transdermal patches (Estradot), or transdermal gel (Oestrogel Pump), there was no significant difference on pregnancy rates.

Research Question: How might time to healthy singleton delivery affect decision-making during infertility treatment?, Design: This was a Delphi consensus investigating expert opinion that comprised three steps. In Step 1, 12 experts developed statements. In Step 2, 27 experts (including 12 from Step 1) voted (online survey) on their agreement/disagreement with each statement (providing reasons). Consensus was reached if ≥66% of participants agreed/disagreed. Statements not reaching consensus were revised and the process repeated until consensus was achieved. In Step 3 details of the final agreed statements were communicated., Results: Twelve statements were developed, and consensus (agreement) was reached on all after one round of voting., Conclusions: Time to healthy singleton delivery should be taken into consideration when making decisions related to infertility treatment, and it is important that fertility treatment is provided in a timely manner, avoiding over- or under-treatment. In all subfertile women <40 years old, IVF outcomes could be optimized by performing up to six single-embryo transfers and certain procedures might reduce time to healthy singleton delivery. These procedures include preimplantation genetic testing for aneuploidies, frozen replacement cycles immediately after failed fresh cycles and use of gonadotrophin-releasing hormone antagonists. Finally, the number of oocytes retrieved should be maximized to increase cumulative live birth rate., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)