Impact of Endometrial Preparation on the Maternal and Fetal Cardiovascular Variables of the First Trimester Combined Screening Test.

The modality of endometrial preparation for the transfer of frozen-thawed embryos may influence maternal and fetal adaptation to pregnancy and could thus impact the results of the first trimester combined screening test. We conducted a retrospective cross-sectional study on singleton pregnancies achieved by embryo transfer of a single frozen-thawed blastocyst, comparing two different endometrial preparation protocols: natural cycle (n = 174) and hormone replacement therapy (HRT) (n = 122). The primary outcome was the risk of preeclampsia at the first trimester combined screening test. Secondary endpoints included variable reflecting fetal cardiac function (nuchal translucency and fetal heart rate), maternal adaptation (median arterial blood pressure-MAP and uterine arteries pulsatility index-UtA-PI), and placentation (pregnancy associated plasma protein A and placental growth factor). The risk of early preeclampsia was comparable in the two groups (38% vs. a 28%, p = 0.12). However, women in the natural cycle group showed lower fetal heart rate (159 [155-164] vs. 164 [158-168], p = 0.002) and higher UtA-PI (0.96 [0.74-1.18] vs. 0.72 [0.58-0.90], p < 0.001). The frequency of a screening test at high risk for aneuploidies was similar. The modality of transfer of frozen-thawed embryos is associated with changes in the variables reflecting maternal and fetal cardiovascular function.

Progesterone levels during ovarian stimulation in segmented ART cycles inversely correlate with normalized birthweight of neonates conceived through subsequent frozen-thawed embryo transfer.

PURPOSE: To evaluate the association between serum progesterone (P) at the day of ovulation trigger and neonatal birthweight in singletons born after frozen-thawed embryo transfer in segmented ART cycles. METHODS: A retrospective multicenter cohort study involving data from patients who achieved uncomplicated pregnancy and term delivery of ART-conceived singleton babies following a segmented GnRH antagonist cycle. The main outcome was birthweight's z-score of the neonate. Univariate and multivariate linear logistic regression analyses were made to investigate the relation of z-score with variables inherent to the patient and to the ovarian stimulation. The variable P per oocyte was created by dividing the value of progesterone at ovulation trigger by the number of oocytes retrieved at oocyte retrieval. RESULTS: A total of 368 patients were included in the analysis. At univariate linear regression, the birthweight z-score of the neonate appeared to be inversely related to both P levels at the ovulation trigger (- 0.101, p = 0.015) and P levels per oocyte at trigger (- 1.417, p = 0.001), while it was directly related to the height of the mother (0.026, p = 0.002) and to the number of previous live births (0.291, p = 0.016). In multivariate analysis, both serum P (- 0.1; p = 0.015) and P per oocyte (- 1.347, p = 0.002) maintained the significant inverse association with birthweight z-score after adjusting for height and parity. CONCLUSIONS: Serum progesterone level on the day of ovulation trigger inversely correlates with normalized birthweight of neonates in segmented GnRH antagonist ART cycles.

Adherence to the Mediterranean diet and the risk of unexpected poor response to ovarian stimulation in IVF cycles.

RESEARCH QUESTION: Can preconception adherence to a Mediterranean diet influence the rate of poor response to ovarian stimulation in IVF cycles? DESIGN: The impact of dietary habits on the success of IVF is controversial. Inconsistencies may be explained by confounders associated with the use of pregnancy as an outcome as well as by a reductionist view of diet that focuses on single components rather than on food patterns. This cross-sectional study analysed adherence to a Mediterranean diet in women with unexpected poor response to ovarian stimulation. Main inclusion criteria were: age 18-39 years, normal weight, preserved ovarian reserve and starting dose of gonadotrophins of 150-225 IU/day. Adherence to the Mediterranean diet was assessed through a Mediterranean diet score (MDS). Unexpected poor ovarian response was defined as the retrieval of ≤3 suitable oocytes. RESULTS: A total of 296 women were included, of whom 47 (15.9%) showed an unexpected poor response. A clear dose-related association with tertiles of MDS was not observed in the univariate analysis. However, in the multivariate analysis, the risk of unexpected poor response was significantly lower for women in the second tertile of MDS compared with the first tertile (adjusted odds ratio [OR] 0.29, 95% confidence interval [CI] 0.11-0.76) and for women in the second and third tertiles, grouped together, compared with the first tertile (adjusted OR 0.34, 95% CI 0.14-0.82). CONCLUSIONS: Low adherence to a Mediterranean diet could be a risk factor for unexpected poor ovarian response.

The neglected role of preimplantation genetic testing for Lynch syndrome.

Preimplantation genetic testing for monogenic/single-gene disorders (PGT-M) is a procedure employed in the field of assisted reproductive technology to avoid the transmission of genetic diseases to the offspring. Hereditary cancer syndromes represent a diffuse and accepted indication for PGT-M, but take-up differs among the different disorders. Its use is markedly lower for the genes causing Lynch syndrome compared with the breast cancer type 1 or 2 susceptibility genes (BRCA1/2), despite the similar prevalence and severity of the two conditions. Reasons to explain this difference have not been explored. First, Lynch syndrome may be more frequently undiagnosed compared with hereditary breast and ovarian cancer syndrome. In addition, the different take-up may be due to different patient perceptions of the conditions and of the management options. Finally, this distinct attitude may depend on the awareness and sensibility of the professionals caring for affected patients. The authors' considerations are, however, speculative, and specific studies aimed at disentangling the causes of the different receptions of PGT-M are warranted to understand how to tackle this gap. In the meantime, we believe that empowerment regarding PGT-M of all individuals with hereditary cancer syndromes, including Lynch syndrome, is ethically due, and plead for a more active involvement of caregivers.

Women's quality of sleep and in vitro fertilization success.

Women undergoing in vitro fertilization (IVF) are emotionally challenged. Anxiety, depression, and sleep disturbances are common complaints. The impact of these symptoms on IVF outcome is however debated. In this study, we aimed at investigating whether sleep quality and psychological health can affect the chances of success of the procedure. Women undergoing IVF were recruited at the time of oocytes retrieval. Women's sleep quality and psychological health was assessed using the Pittsburgh Sleep Quality Index (PSQI), the Fertility Problem Inventory (FPI), and the Hospital Anxiety and Depression Scale (HADS). Baseline characteristics and results of the three scales were compared between women who did and did not succeed. Overall, 263 women were included, of whom 81 had a clinical pregnancy (31%). As expected, successful women were younger, and their ovarian reserve was more preserved. FPI and HADS scores did not differ. Conversely, a statistically significant difference emerged for the PSQI score, the median [interquartile range] in pregnant and non-pregnant women being 4 [3-5] and 5 [3-7], respectively (p = 0.004). The crude and adjusted OR of pregnancy in women with a PSQI > 5 (indicating impaired sleep quality) was 0.46 (95% CI 0.25-0.86, p = 0.02) and 0.50 (95% CI: 0.26-0.94, p = 0.03), respectively. In conclusion, low sleep quality is common in women scheduled for IVF and could influence the success of the procedure.

Clinical implications of first-trimester ultrasound dating in singleton pregnancies obtained through in vitro fertilization.

BACKGROUND: In pregnancies obtained by in-vitro fertilization (IVF) the exact day of conception is known. For that reason, IVF pregnancies are currently dated according to the day of oocytes retrieval and consequent embryo transfer. The aim of the present study is to determine whether the knowledge of the exact day of conception in IVF pregnancies is a sufficient argument against dating these pregnancies by first trimester ultrasound measurement of the crown-rump length (CRL), as it is recommended in natural conceptions. METHODS: A retrospective study was performed, including all women with singleton pregnancies conceived by IVF who underwent the first-trimester ultrasound scan for the screening of aneuploidies between January 2014 and June 2019. For each pregnancy GA was determined using two alternative methods: one based on the date of embryo transfer (GAIVF), and one based on ultrasound measurement of CRL (GAUS). GA were compared to search for any discrepancy. The impact of pregnancy dating on obstetric outcome was evaluated. RESULTS: Overall, 249 women were included. Comparing GAUS and GAIVF, a median difference of 1 [0 - 2] days emerged (p<0.001), with GAUS being in advance compared to GAIVF. This discrepancy persisted when subgroups were analyzed comparing different IVF procedures (conventional IVF versus ICSI, cleavage versus blastocyst transfer, frozen versus fresh transfer). No impact of the dating method on obstetric outcomes was observed, being no differences in the rate of preterm birth or abnormal fetal growth. CONCLUSIONS: In IVF pregnancies GAUS and GAIVF are not overlapping, since GAUS is mildly greater than GAIVF. This could be due to an anticipated ovulation and fertilization in IVF pregnancy, rather than an accelerated embryo development. For that reason, it would be appropriate to date IVF pregnancies according to GAUS, despite a known date of conception, to re-align IVF pregnancies to natural ones.

Effect of letrozole on follicular fluid steroids concentrations in cancer patients undergoing oocyte cryopreservation.

PURPOSE: To investigate the impact of letrozole administration on follicular steroid hormones during controlled ovarian hyperstimulation for fertility preservation. METHODS: One hundred and nineteen women with cancer undergoing oocytes retrieval for fertility preservation were recruited. All women underwent ovarian hyperstimulation according to a random start protocol. Those with hormone-sensitive tumors also received letrozole, an aromatase inhibitor aimed at keeping peripheral estrogen levels low. At the time of oocytes retrieval, a sample of follicular fluid was collected and frozen. All samples were assayed concomitantly after thawing, by liquid chromatography tandem mass spectrometry. The concentration of 15 steroid hormones was determined and results were compared between women who did and did not receive letrozole. RESULTS: Fifty-two women were treated with letrozole, while 67 were not. Statistically significant differences emerged for 12 of the 15 tested steroids. They were the following: cortisol, 11-deoxycortisol, 21-deoxycortisol, dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), estradiol, androstenedione, testosterone, dihydrotestosterone (DHT), 17-hydroxyprogesterone, progesterone and corticosterone. The most striking differences were observed for testosterone that showed a more than 200-time increase in women receiving letrozole. Estradiol was conversely reduced to a third. CONCLUSIONS: The endocrine microenvironment surrounding oocytes is markedly perturbed by the concomitant assumption of letrozole. Robust clinical evaluation is pressingly needed to rule out any detrimental effect on the chance of live birth with the use of these oocytes.

Satisfaction and usability of the recombinant chorionic gonadotropin prefilled pen: a survey in Italy.

BACKGROUND: Due to high purity, recombinant human chorionic gonadotropin (hCG) is suitable for subcutaneous injection, and hence for self-administration, in assisted reproduction. To increase usability and reduce the risk of dosing errors, a prefilled pen was produced. We investigated the ease of administration and satisfaction with the product amongst patients and healthcare professionals. METHODS: A survey was conducted amongst women with infertility who underwent in vitro fertilization treatments with recombinant hCG to trigger ovulation in various clinics in Italy. RESULTS: A total of 276 Italian women were interviewed. The median score of preference for the prefilled pen in comparison with hCG powder to be reconstituted in the solvent was rated as 9 (range 8-10), and 125 women answered that the prefilled pen had major advantages. Reasons for preference of the prefilled pen were linked to ease of use and safety: avoidance of dosage mistakes and of concern of such, ease of administration, certainty that the drug is correctly taken, safe administration and no anxiety. The procedure for recombinant hCG administration through the prefilled pen was judged as easy by 80% of respondents, with a median score of 9 (range 8-10) for easiness on a 1-10 scale. Out of 276 respondents, 249 (90%) had no problem with the injection. CONCLUSION: Overall, the respondents reported a favourable perception of the prefilled pen with hCG, which was reported to be easy to use and perceived to prevent dosage mistakes.

Endometrial preparation does not affect the risk of hypertensive disorders of pregnancy in low-risk women undergoing frozen embryo transfer.

OBJECTIVE: Frozen embryo transfer (FET) is associated with a higher risk of hypertensive disorders in pregnancy. The objective of the present study is to evaluate the effect of different protocols of endometrial preparation on the risk of these disorders. METHODS: We conducted a retrospective cohort study on 594 singleton pregnancies achieved by embryo transfer of single frozen-thawed blastocysts. Women with preexisting risk factors for hypertensive disorders were excluded. Women were divided into two groups according to the endometrial preparation protocol: either natural cycle (n = 495) or programming cycle with hormonal replacement therapy (n = 97). The primary outcome was the frequency of hypertensive disorders in pregnancy: specifically, gestational hypertension and preeclampsia. RESULTS: No differences emerged between women following the natural cycle and those following the programming cycle in the frequency of gestational hypertension (5 vs. 4%) and preeclampsia (1.1 vs. 1.2%). No impact emerged also after multivariate analyses. CONCLUSIONS: Women receiving hormonal replacement therapy have the same risk of gestational hypertension and preeclampsia as women following natural cycles when considering low-risk singleton pregnancies.

Fertility Counseling in Survivors of Cancer in Childhood and Adolescence: Time for a Reappraisal?

Genetic predisposition could have an important role in the pathogenesis of cancers in children and adolescents. A recent study by our group showed that, among female survivors of cancers in childhood and adolescence, the proportion of cases involving a possible genetic predisposition was sizable (at least one in five). Our sample is too small to be representative of the general population, but it gave us an opportunity to reappraise this issue. Women with a genetic predisposition can transmit the risk of cancer to their offspring, and their awareness of this may influence their reproductive and fertility preservation choices. In our experience, a predisposition to cancer receives little attention in the fertility counseling and decision-making process unless a patient already has a definitive molecular diagnosis of a hereditary cancer syndrome. We feel it is essential to empower women on this issue, particularly as there are ways to overcome the problem, including preimplantation genetic testing (PGT-M) in definitively diagnosed cases, egg donation and adoption. In the context of fertility counseling for survivors of cancer in childhood and adolescence who have reached adulthood, the risk of transmitting a predisposition to cancer should be discussed with patients, if relevant and desired.

Fertility preservation in childhood and adolescent female tumor survivors.

OBJECTIVE: To assess the proportion of female childhood and adolescent tumor survivors who could benefit from oocyte cryopreservation. DESIGN: Case series of female childhood and adolescent tumor survivors referred for fertility counseling. SETTING: A referral cancer center and an infertility unit of an academic hospital. PATIENT(S): Young female childhood and adolescent tumor survivors who received gonadotoxic treatments. INTERVENTION(S): Patients were prescribed tests of ovarian reserve and a personalized counseling was given. Oocyte cryopreservation was considered in subjects aged ≥18 years who were diagnosed with diminished ovarian reserve (DOR) (antimüllerian hormone level <2 ng/mL or total antral follicle count ≤10). MAIN OUTCOME MEASURE(S): Rate of women with DOR who stored their oocytes. RESULT(S): Ninety out of 126 evaluated women completed the assessments. We documented preserved ovarian reserve, DOR, and premature ovarian insufficiency in 36 (40%), 35 (39%), and 19 (21%) cases, respectively. Overall, 13 subjects with DOR were eligible for oocyte cryostorage, of whom 9 (69%) underwent the procedure. Considering the whole cohort of evaluated young women (n = 90), the rate of those who had egg freezing was 10%. Finally, nine women started seeking pregnancy after the counseling (six with DOR), and seven of them became pregnant. When the data were analyzed separately according to most gonadotoxic treatments, considerable differences emerged but the evidence did not support the idea that counseling should be restricted to particular subgroups of women. CONCLUSION(S): Ovarian reserve impairment is common in female childhood and adolescent tumor survivors. Postcancer oocyte cryopreservation may be part of the armamentarium of fertility preservation options.

Trend of medically induced monozygotic twin deliveries according to age, parity, and type of assisted reproductive technique during the period 2007-2017 in Lombardy Region, Northern Italy: a population-based study.

PURPOSE: The risk of monozygotic (MZT) twinning is increased in pregnancies after assisted reproductive technologies (ART). However, determinants remain poorly understood. To shed more light on this issue, we analyzed the estimated frequency of MZT twins from ART in Lombardy, Northern Italy, during the period 2007-2017. METHODS: This is a population-based study using regional healthcare databases of Lombardy Region. After having detected the total number of deliveries of sex-concordant and sex-discordant twins from ART, we calculated MZT rate using Weinberg's method. Standardized ratios (SRs) and corresponding 95% confidence intervals (CI) of MZT deliveries, adjusted for maternal age, were computed according to calendar period, parity, and type of ART. RESULTS: On the whole, 19,130 deliveries from ART were identified, of which 3,446 were twins. The estimated rate of MZT births among ART pregnancies was higher but decreased over time (p-value = 0.03); the SRs being 1.33 (95% CI: 1.18-1.51), 0.96 (95% CI: 0.83-1.11), and 0.92 (95% CI: 0.79-1.07) for the periods 2007-2010, 2011-2014, and 2015-2017, respectively. The SRs of MZT among women undergoing first-level techniques, conventional in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI) were 0.47 (95% CI: 0.38-0.57), 1.02 (95% CI: 0.88-1.17), and 1.43 (95% CI: 1.27-1.61) (p-value < 0.0001). The ratio of MZT births was significantly higher in women younger than 35 years (p-value < 0.0001) and slightly higher among nulliparae (p-value < 0.0001). CONCLUSION: Despite a reduction of MZT rate from ART over the time, the risk remains higher among ART pregnancies rather than natural ones. Younger women and women undergoing ICSI showed the highest risk of all.

Variables affecting long-term usage rate of sperm samples cryopreserved for fertility preservation in cancer patients.

BACKGROUND: Previous evidence highlighted that only a minority of men who banked their semen before cancer therapies subsequently used their frozen samples. This may question the economical validity of sperm cryopreservation programmes. However, in most contributions, the duration of follow-up was insufficient to draw robust information on the real rate of use. OBJECTIVES: To shed more light on the potential benefits of cryopreservation programmes. MATERIALS AND METHODS: Men who cryopreserved their semen in a public hospital for a diagnosis of cancer between 1986 and 2009 were retrospectively reviewed. The rate of use as well as the possible determinants was investigated. RESULTS: The median time of follow-up was 12 [IQR: 7-16] years. One hundred forty-four patients out of 1,524 (9.4%, 95%CI: 8.1%-11.0%) used their frozen samples of whom 64% were azoospermic. The rate of men achieving parenthood with frozen semen was 46%. Predictive factors of use were older age at the time of storage, lower sperm count at the time of storage and a diagnosis of testicular cancer. The impact of this latter factor was also supported by the lower frequency of azoospermia after cancer treatment in these patients. DISCUSSION: Cost-beneficial studies are warranted to assess and possibly improve the economical validity of sperm banking. CONCLUSION: The usage rate of frozen sperm in cancer patient is low, even extending the duration of follow-up.

Risk Factors for Monozygotic Twins in IVF-ICSI Cycles: a Case-Control Study.

In vitro fertilization (IVF) is associated with a higher incidence of monozygotic twin pregnancies, which are known to be burdened by a higher risk of main obstetric complications. The reasons behind this association are still unclear. In the present study, we therefore investigate the risk factors for monozygotic twinning in pregnancies achieved by IVF. We conducted a multicenter retrospective case-control study. All IVF cycles performed between 2014 and 2019 at the infertility units of two Italian academic institutes were retrospectively reviewed. Only pregnancies obtained with single embryo transfer were eligible. A total of 50 monozygotic twin pregnancies (cases) were identified and matched in a 1:5 ratio to 250 singleton pregnancies (controls) by study center and study period. Monozygotic twin pregnancies were diagnosed by ultrasound. Women experiencing miscarriage could be included provided that the pregnancy loss occurred after a definitive diagnosis of monozygotic twin pregnancy. Demographic, clinical, and embryological characteristics were retrieved from patients' charts. Overall, the incidence of monozygotic twin pregnancies was 1.2% (50 out of 4016 single embryo transfers). At univariate analyses, statistically significant differences emerged for BMI, peripheral levels of estradiol and progesterone at the time of hCG administration, total number of retrieved suitable oocytes, freezing-thawing cycles, and assisted hatching. After performing a multivariate logistic analysis, only assisted hatching remained significantly associated with monozygotic twinning (adjusted odds ratio 2.32, 95%CI 1.03-5.25). Blastomere separation during the passage through this artificial hole or interference with the signaling pathway within the embryo could be the mechanisms involved.

The role of diet in unexpected poor response to ovarian stimulation: a cross-sectional study.

RESEARCH QUESTION: Is there an association between diet and poor ovarian response to ovarian stimulation in women with normal biomarkers of ovarian reserve? DESIGN: Women eligible for IVF at an Academic Fertility Center were invited to participate in this prospective cross-sectional study. The main inclusion criteria were age 18-39 years, body mass index 18-25 kg/m2, preserved ovarian reserve (antral follicle count 10-22 or anti-Müllerian hormone concentration 2-5 ng/ml) and a starting dose of gonadotrophins of 150-225 IU/day. Information on diet was obtained using a validated food frequency questionnaire. 'Unexpected poor ovarian response' was defined as the retrieval of three or fewer suitable oocytes. A logistic regression model was used to adjust for confounders. RESULTS: Out of the 303 women enrolled in the study, 48 (16%) showed an unexpected poor ovarian response. The frequency of poor responders increased with increasing glycaemic load, carbohydrate intake and fibre intake. When comparing the third with the first tertile (reference), the adjusted odds ratios for these were 3.91 (95% confidence interval [CI] 1.11-13.83, P = 0.04), 4.78 (95% CI 1.23-18.51, P = 0.02) and 6.03 (95% CI 1.18-30.77, P = 0.07), respectively. CONCLUSIONS: Elevated dietary glycaemic load as well as carbohydrate intake and fibre intake is significantly associated with unexpected poor ovarian response. Future interventional studies should clarify whether dietary modification might restore normal response.

Risk factors for monozygotic twinning after in vitro fertilization: a systematic review and meta-analysis.

OBJECTIVES: To establish the risk factors for monozygotic twin (MZT) and monochorionic twin (MCT) pregnancies after in vitro fertilization (IVF). DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Women who achieved MZT and non-MZT pregnancies through IVF. INTERVENTION(S): Systematic search of Medline from January 1995 to October 2018 with cross-checking of references from relevant articles in English. MAIN OUTCOME MEASURE(S): Possible risk factors for MZT or MCT pregnancies after IVF, comprising extended embryo culture, insemination method (conventional IVF and intracytoplasmic sperm injection [ICSI]), embryo biopsy for preimplantation genetic testing for aneuploidies or for monogenic/single-gene defects (PGT-A or PGT-M) programs, assisted hatching (AH), oocytes donation, female age, and embryo cryopreservation. RESULT(S): A total of 40 studies were included. Blastocyst transfer compared with cleavage-stage embryo transfer, and female age <35 years were associated with a statistically significant increase in the MZT and MCT pregnancy rate after IVF: (23 studies, OR 2.16, 95% CI, 1.74-2.68, I2=78%; 4 studies, OR 1.29; 95% CI, 1.03-1.62, I2=62%; and 3 studies, OR 1.90, 95% CI, 1.21-2.98, I2=59%; 2 studies, OR 2.34; 95% CI, 1.69-3.23, I2=0, respectively). Conventional IVF compared with ICSI and assisted hatching were associated with a statistically significantly increased risk of MZT pregnancy (9 studies, OR 1.19, 95% CI, 1.04-1.35, I2=0; 16 studies, OR 1.17, 95% CI, 1.09-1.27, I2=29%, respectively). Embryo biopsy for PGT-A or PGT-M, embryo cryopreservation, and oocytes donation were not associated with MZT pregnancies after IVF. CONCLUSION(S): Blastocyst transfer is associated with an increased risk of both MZT and MCT pregnancies after IVF. Further evidence is needed to clarify the impact of female age, insemination method and AH on the investigated outcomes.

First trimester combined screening test in pregnancies derived from blastocyst transfer.

OBJECTIVE: To investigate whether first trimester combined screening for major fetal trisomies is influenced by assisted reproduction techniques from blastocyst transfer, with or without cryopreservation. STUDY DESIGN: retrospective case-control analysis involving 298 singleton pregnancies with euploid fetuses recruited between 2012 and 2014. Forty-seven women conceived with fresh blastocysts from in vitro fertilization cycles (fresh-blasto), 51 with frozen-thawed blastocysts (frozen-blasto) and 200 were natural conceptions (controls). All cases underwent ultrasound assessment at 11(+0)-13(+6) weeks with measurements of crown rump length, nuchal translucency, free ß-hCG and PAPP-A concentrations. The outcome of pregnancy was recorded (gestational age at birth, birth weight, obstetric complications). RESULTS: Baseline characteristics and pregnancy outcomes did not differ substantially among the study groups. The median delta nuchal translucency was significantly higher both in frozen-blasto group (median: 0.27mm; Interquartile Range [IQR]: 0.02-0.44; p<0.001) and in fresh-blasto group (median: 0.17mm; IQR: 0.04-0.39; p=0.014) as compared to control group (median: 0.06mm; IQR: -0.08 to 0.20), whereas it was not different in the frozen-blasto compared to the fresh-blasto group. The median free ß-hCG multiples of the median (MoMs) was significantly higher both in frozen-blasto group (median 1.15; IQR 0.83-2.11; p=0.001) and in fresh-blasto group (median 0.95; IQR 0.52-1.48; p=0.001) as compared to control group (median 0.99; IQR 0.57-1.26), and it was also higher in frozen-blasto group compared to fresh-blasto group (p<0.001). The three groups showed no significant differences in the median PAPP-A MoMs. The median delta crown rump length was also not significantly different among the three groups. CONCLUSIONS: in assisted reproduction technique pregnancies from blastocyst transfer, with or without cryopreservation, both the nuchal translucency measurement and free ß-hCG concentration are higher as compared to spontaneous conceptions, whereas PAPP-A does not show any significant difference. These features are apparently unrelated to the outcome of pregnancy and may be due to alterations or delays in embryogenesis or placentation with potential relevance for the screening test performance.

Hyperreactio luteinalis: timely diagnosis minimizes the risk of oophorectomy and alerts clinicians to the associated risk of placental insufficiency.

Hyperreactio luteinalis (HL) is a rare benign condition complicating pregnancy with multicystic bilateral ovarian enlargement, increased serum ßhCG levels and spontaneous regression after delivery. HL has been associated with complications of pregnancy and the aim of our research was to review the literature, and add a new unpublished case from our group. We searched the internet-based medical databases for case reports and case series of hyperreactio luteinalis and we evaluated diagnostic path, treatment and outcome of pregnancies. We found 96 cases of HL from 1955 to 2013. HL was asymptomatic in 28% of cases but in 72% of patients there were symptoms like lower abdominal pain, nausea and vomiting, ascites and signs of virilization. Suspicion of malignancy was raised in 38% of cases. Surgical treatment of various types was performed in 48% of cases, with oophorectomy in 40% of this group. Several complications were associated with HL, in particular preeclampsia (PE) occurred in 24% of cases and fetal growth restriction (FGR) in 12%. Mean gestation at delivery was 35 weeks (range 25-42). Although preoperative diagnosis occurred in most cases, suspicion of malignancy was extensive, as was oophorectomy, demonstrating suboptimal understanding of the underlying physiopathology. We propose a diagnostic algorithm for this condition. Training of obstetricians in making the correct diagnosis may prevent unnecessary oophorectomies and may lead to early diagnosis and correct management of associated complications.