Abnormal implantation after fresh and frozen in vitro fertilization cycles.

OBJECTIVE: To determine whether fresh embryo transfers are at a higher risk of abnormal implantation compared with frozen embryo transfers while accounting for the embryo stage at transfer. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): We used data from the Society for Assisted Reproductive Technologies to identify all fresh and frozen autologous IVF cycles from 2004-2013 resulting in a positive pregnancy test. The cycles were parameterized into a four-level predictor of [1] fresh blastocyst transfer, [2] fresh non-blastocyst transfer, [3] frozen blastocyst transfer, and [4] frozen non-blastocyst transfer. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We examined a composite outcome of abnormal implantation, defined as biochemical pregnancy, ectopic/heterotopic pregnancy, and first-trimester pregnancy loss. Regression modeling was performed with repeated measures multivariable logistic regression, adjusted for age, parity, number of embryos transferred, infertility diagnosis, and calendar year of treatment. RESULT(S): Of 509,938 cycles analyzed, 31.8% resulted in abnormal implantation. Compared with a fresh blastocyst transfer, a fresh non-blastocyst transfer had a 22% increase risk of abnormal implantation, a frozen blastocyst transfer had a 36% increase risk, and a frozen non-blastocyst transfer had a 57% increase risk. When individual outcomes were analyzed, fresh embryo transfers had a lower risk of biochemical pregnancy and pregnancy loss but a higher risk for ectopic/heterotopic pregnancy. CONCLUSION(S): Fresh blastocyst transfers had the lowest overall risk of abnormal implantation but a higher risk of ectopic/heterotopic pregnancy. Although embryo cryopreservation is indicated in certain treatment cycles, elective embryo cryopreservation may not be the optimal strategy to adopt for all cycles.

Chronic endometritis in women with recurrent early pregnancy loss and/or fetal demise.

OBJECTIVE: To assess the prevalence of chronic endometritis in women with a history of recurrent early pregnancy loss (REPL) and/or fetal demise (FD). DESIGN: Observational cohort study using prospectively collected data. SETTING: Recurrent pregnancy loss program in an academic medical center. PATIENT(S): Three hundred ninety-five women with a history of two or more pregnancy losses of less than 10 weeks' size or a fetal demise of 10 or more weeks' size. INTERVENTION(S): All women had an endometrial biopsy. Chronic endometritis was treated with antibiotics, and a second endometrial biopsy was recommended as a "test of cure." MAIN OUTCOME MEASURE(S): Subsequent live-birth rate (LBR). RESULT(S): The overall prevalence of chronic endometritis was 9% (35/395) in this cohort; 7% (21/285) in the REPL group, 14% (8/57) in the FD group, and 11% (6/53) in the combined REPL/FD group. The cure rate was 100% after a course(s) of antibiotics. The subsequent cumulative LBR was 88% (21/24) for the treated chronic endometritis group versus 74% (180/244) for the group without chronic endometritis. The per-pregnancy LBR for the treated chronic endometritis group was 7% (7/98) before treatment versus 56% (28/50) after treatment. CONCLUSION(S): There was a high prevalence of chronic endometritis in this cohort. The test of cure was 100% with antibiotics. Subsequent LBRs after treatment were encouraging.

Efectos de la selección y de la superovulación en las pérdidas gestacionales de ratonas CF1 / Effects of selection and superovulation on gestational losses in CF1 mice

En un par de líneas de ratones seleccionadas para alto (s') y bajo peso (s), originadas a partir de una población no seleccionada de la cepa CF1 (t), se modificó la estructura ovárica. El diámetro de los folículos ováricos y el número de folículos y de cuerpos lúteos se incrementaron en las hembras de la línea s', sin expresarse en un mayor tamaño de camada al nacimiento, posiblemente, por un aumento de las pérdidas gestacionales. Se probó si los efectos conjuntos de la selección de peso a largo plazo y de la estimulación ovárica incrementaban las pérdidas gestacionales. Se utilizaron dos grupos de hembras por línea: sin y con estimulación ovárica (5UI de eCG y 5UI de hCG). Las hembras se sacrificaron a las 56-72 hs y a los 7 días postservicio y después de la primera parición. Se observaron los números de cuerpos lúteos (CL), embriones (E) y sitios de implantación (SI) y el tamaño de camada al nacimiento (TC). Se estimaron las pérdidas totales (PT) y las pérdidas de cuerpos lúteos (PCL), de embriones (PE) y de fetos (PF). Los promedios de CL, E, SI y TC variaron en el mismo sentido de la selección practicada y fueron significativamente mayores (P<0,05) para las hembras estimuladas, a excepción de TC. La línea s' tuvo un potencial reproductivo superior pero un mayor costo biológico (mayor PT y más tardía) cuando se la comparó con las otras líneas. La estimulación ovárica produjo menores eficiencias reproductivas totales para las tres líneas y pérdidas gestacionales mayores y más tardías, principalmente de SI. Las hembras de la línea no seleccionada (t), no estimuladas, con pesos intermedios, parieron un mayor número de crías, partiendo de un número intermedio de CL, E y SI, con una menor y más temprana mortalidad embrionaria, demostrando ser las más eficientes desde el punto de vista reproductivo y productivo.

The ovarian structure was modified as a consequence of weight selection in a pair of mouse lines selected for high (s') and low weight (s). Lines were founded from an unselected population of CF1 strain (t). The follicle diameter and the number of the ovarian follicles and the corpora lutea were higher in s' females, but they did not reach a larger litter size at birth, may be, by an increase in the gestational losses. In these lines, the co-effects of long-term weight selection and ovarian stimulation were tested to evaluate if they increased gestational losses. Two groups of females per line were employed: without and with ovarian stimulation (5UI of eCG and 5UI of hCG). Females were slaughtered at 56-72hs and at 7 days post-breeding and after first parturition. The number of corpora lutea (CL), embryos (E) and implantation sites (SI), and litter size at birth (TC) were observed. Total losses (PT) and corpora lutea (PCL), embryo (PE) and fetus (PF) losses were estimated. Mean CL, E, SI and TC varied in the same direction of the selection made and they were significantly higher (P<0.05) in stimulated females, though not for TC. Line s' had a higher reproductive potential but a greater biological cost (higher and later gestational mortality) when compared with the other lines. Ovarian stimulation produced lower total reproductive efficiencies for the three lines and higher and later gestational losses, mainly for implantation sites. Females from unselected line (t), without ovarian stimulation, with intermediate weights, bore larger litters, starting from an intermediate number of CL, E and SI, with a lower and earlier embryo mortality, showing to be the most efficient from a reproductive and productive point of view.

The expanded amnion sign: evidence of early embryonic death.

OBJECTIVE: The purpose of this study was to assess the positive predictive value for confirming early embryonic death in the clinical scenario wherein an embryo is identified without a visible heartbeat, but the embryonic crown-rump length (CRL) is 5 mm or less. METHODS: We conducted a retrospective study of 882 first-trimester sonograms with abnormal findings among women who were threatening to abort. Eight hundred six met the inclusion criteria. RESULTS: Among the cohort of 806 cases, 520 (64.5%) had an identifiable embryo, and 255 of those with an identifiable embryo had a visible amnion (49.0%). One hundred sixteen of the 255 with a visible amnion and an identifiable embryo without a heartbeat had a CRL that measured 5 mm or less (45.5%). The CRL of these embryos ranged from 1.7 to 5.4 mm (ie, when rounded to the nearest millimeter, these embryos would be 5 mm) with the breakdown as follows: those measuring less than or equal to 3.4 mm (n = 28), those measuring 3.5 to 4.4 mm (n = 45), and those measuring 4.5 to 5.4 mm (n = 43). Eight of these 116 patients did not have any documented follow-up. In the remaining 108 patients, pregnancy failure was confirmed. CONCLUSIONS: We conclude that any embryo that is surrounded by an amnion and that also lacks a heartbeat has unfortunately but definitively died. This is equally true for embryos measuring less than 5 mm in CRL.

Taxas de serviço, concepção e prenhez de vacas nelore tratadas com gonadotrofina coriônica humana e 17?-estradiol após a inseminação artificial em tempo fixo / Service, conception and pregnancy rates of nelore cows treated with human corionic gonadotropin and estradiol-17? after timed artificial insemination

Avaliaram-se estratégias para reduzir a mortalidade embrionária em bovinos. Vacas Nelore (Bos taurus indicus) foram inseminadas em tempo fixo (IATF - D0) após o protocolo GnRH/PGF2a/GnRH e divididas nos grupos: Controle (Gc; n=55), hCG (GhCG; n=55) recebeu 3000 UI da hCG no D5 , E2 (GE2; n=55) recebeu 5 mg de 17?-Estradiol (E2) no D12 e hCG/E2 (GhCG/E2; n=55) recebeu 3000 UI da hCG no D5 e 5mg do E2 no D12. A IATF foi o 1o dia da estação de reprodução de 64 dias. Usou-se o teste do c2 para comparar as taxas de serviço (TS), concepção (TC) e prenhez à IATF (TPIATF), às IAs de repasse e acumuladas. A TS e a TC das IAs de repasse não diferiu (P>0,10). Houve diferenças nas TPIATF (P<0,05), pois a TPIATF do GE2 (5,4%) foi a mais baixa e a do Gc (34,5%) e GhCG (36,5%) tenderam (P<0,10) ser maiores que a do GhCG/E2 (18,2%). Não houve efeito da hCG sobre as taxas de prenhez. O E2 reduziu a TPIATF e ao final da estação as vacas que receberam o E2 (GE2 + GhCG/E2) tiveram TPacum (66,4%) mais baixa (P<0,05) de que aquelas (80,9%) que não receberam (GC + GhCG). Em conclusão, as estratégias adotadas de manipulação luteínica ou folicular não aumentaram as taxas de prenhez em vacas Nelore após uma IATF.

Strategies to reduce embryo mortality in cattle have been evaluated. Nelore (Bos taurus indicus) cows were submitted to timed artificial insemination (TAI - D0) after a GnRH/PGF2a/GnRH protocol. Cows were divided in the following groups: Control (Gc; n=55), hCG (GhCG; n=55) received 3000 IU of hCG on D5 , E2 (GE2; n=55) received 5 mg of Estradiol-17b (E2) on D12 and hCG/E2 (GhCG/E2; n=55) received hCG on D5 and E2 on D12. TAI represented the 1st day of a 64 day breeding season. The c2 test was applied to compare mating rate (MR), conception rate (CR) and pregnancy rate (PR) to TAI and AIs after natural estrus within the season as well as their accumulated figures at the end of the season. MR and CR for AIs within season did not differ (P>.10). PR to TAI differed (P<.05) among groups. GE2 showed the lowest rate (5,4%). Gc (34.5%) and GhCG (36.5%) tended (P<.10) to be higher than GhCG/E2 (18.2%). There was no effect of hCG on pregnancy rates. E2 reduced PR to TAI and at the end of season which means that cows receiving E2 (GE2 + GhCG/E2) had lower (66.4%; P<.05) PR than cows not receiving E2 (GC + GhCG; 80.9%). In conlusion, the strategies to manipulate luteal and follicular function herein tested did not increase pregnancy rates in Nelore cows submitted to a TAI.

[Influence of nitric oxide synthase inhibitors on embryonic destructions and morphological features in pre- and postimplantation mouse embryos]. / Vliianie ingibitorov NO-sintaz na pokazateli émbrional'noi gibeli pre- i postimplantatsionnykh émbrionov myshei.

Nitric oxide is an important intraovarian regulatory factor. The periimplantation period is a critical phase in mouse development. Although it was shown that nitric oxide plays an essential role during gestation, its role in the preimplantation period is not yet fully clear. We studied the involvement of nitric oxide in developmental competence (embryonic defects and morphology of pre- and postimplantation embryos) using nitric oxide synthase inhibitors, which suppress all forms of nitric oxide synthase, and female mice, to which the inhibitors had been administered before their mating with intact males. The level of mortality of pre- and postimplantation embryos in females mated to intact males increased soon after the administration of inhibitors. Studies of the morphology of embryos have shown that there was a delay in embryogenesis at the stages of cleavage and gastrulation. The results obtained suggest that nitric oxide is a potent regulator of embryonic differentiation, specifically in pre- and postimplantation mouse embryos.

[Influence of combined microinjection of gene engineering construct and endonuclease on preimplantation development of mouse embryos in vitro]. / Vliianie sovmestnoi mikroin''ektsii genno-inzhenernoi konstruktsii i éndonukleazy na doimplantatsionnoe razvitie émbrionov myshi in vitro.

We studied the influence of combined microinjection of a gene engineering construct and site-specific endonuclease Sal in the pronucleus on preimplantation development of (CBA x C57BL)F1 mouse embryos in vitro. The rate of survival of the embryos was estimated according to their capacity to develop until the blastocyst stage and hatch from zona pellucida. The results obtained suggest that the microinjection of exogenous DNA jointly with endonuclease SalI at concentrations from 0.1 to 0.01 U/microl decreased reliably the rate of survival, as compared to the control (p < 0.05 and p < 0.01, respectively). However, a decrease of endonuclease SalI concentration in the injection mixture to 0.01 U/microl enhanced the capacity of mouse embryos to develop until the blastocyst stage and hatch from zona pellucida, as compared to the embryos microinjected with exogenous DNA and endonuclease SalI at a higher concentration.

Sonography: dizygotic twin survival in early pregnancy.

It has been suggested that losses of twin conceptuses in very early pregnancy are high, and that for every liveborn twin pair there are a further 10-12 twin pregnancies that end up as a singleton birth. Here we show that in a group of women who had double-ovulated and conceived, the probability of the second egg also becoming fertilized and developing is 20-30% - which is comparable to the probability of conception and survival of a single conceptus. We conclude that the presence of one embryo does not affect the development of its twin.