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1.
A couple with male infertility due to non-obstructive azoospermia were referred to the fertility centre for treatment. Testicular biopsy was performed on the male partner and testicular samples were frozen. The female partner underwent ovarian stimulation and 31 mature oocytes were recovered by ultrasound-guided vaginal aspiration. Twelve oocytes were cryopreserved by the Cryotop vitrification method and 19 oocytes were inseminated by intracytoplasmic sperm injection (ICSI) using frozen–thawed testicular spermatozoa. Nine out of 19 oocytes were fertilized and the resulting embryos were cryopreserved by slow freezing. Four months later, two out of six thawed embryos were transferred, but no pregnancy resulted. One year later, the couple decided to attempt pregnancy using vitrified oocytes and frozen testicular spermatozoa. Six vitrified–warmed oocytes were injected with frozen–thawed testicular spermatozoa and four were fertilized. On the day of transfer, two cleavage stage embryos (4-cell, 2-cell) were obtained. Serum β-HCG test 14 days after embryo transfer was positive. Hormonal support for the established pregnancy was maintained with oestradiol and progesterone orally until 12 weeks of gestation. A healthy baby boy weighing 3.09 kg was delivered by elective Caesarean section at 38 weeks of gestation. This case report demonstrates that oocyte cryopreservation by the Cryotop vitrification method does not compromise oocyte developmental competence.  相似文献   

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This study reports two clinical pregnancies and one live birth following the transfer of vitrified blastocysts developed from oocytes with neither zona pellucida nor corona cells. Two zona-free oocytes obtained from two patients of advanced maternal age undergoing minimal stimulation were normally fertilized after intracytoplasmic sperm injection. In case 1, all four blastomeres of the zona-free embryo were loosely associated and inserted back into ruptured zona on day 2. Zona-free embryo from case 2 had tight contacts between blastomeres and was cultured without zona. Both embryos derived from zona-free oocytes progressed to blastocyst stage and were cryopreserved by vitrification. When patients came back for a cryopreserved embryo transfer, both vitrified blastocysts survived warming. In case 1, transfer of a warmed blastocyst with reconstructed zona resulted in a clinical pregnancy that ended in a spontaneous abortion at 22 weeks. In case 2, live birth was achieved with a normal healthy baby (male) weighing 2381 g at 40 weeks’ gestation. This report emphasizes the importance of maintenance of normal cell arrangement on the subsequent embryonic development for a zona-free oocyte. Zona-free oocytes may provide a valuable source of embryos for infertility patients, especially for those with a limited number of oocytes.In this study, we report two clinical pregnancies and one live birth following the transfer of vitrified blastocysts developed from oocytes with neither zona pellucida nor corona cells. Two zona-free oocytes obtained from two patients of advanced maternal age undergoing minimal stimulation were normally fertilized after intracytoplasmic sperm injection. In case 1, all four blastomeres of the zona-free embryo were loosely associated and inserted back into ruptured zona on day 2. Zona-free embryo from case 2 had tight contacts between blastomeres and was cultured without zona. Both embryos derived from zona-free oocytes progressed to blastocyst stage and were cryopreserved by vitrification. When patients came back for a cryopreserved embryo transfer, both vitrified blastocysts survived warming. In case 1, transfer of a warmed blastocyst with reconstructed zona resulted in a clinical pregnancy that ended in a spontaneous abortion at 22 weeks. In case 2, live birth was achieved with a normal healthy baby (male) weighing 2381 g at 40 weeks’ gestation. Our report emphasizes the importance of maintenance of normal cell arrangement on the subsequent embryonic development for a zona-free oocyte. Zona-free oocytes may provide a valuable source of embryos for infertility patients, especially for those with a limited number of oocytes.  相似文献   

4.
ObjectiveTo report a birth of a healthy girl after long-term oocyte cryopreservation by slow cooling in sodium depleted medium.DesignClinical application.SettingUniversity Affiliated, Private IVF center.PatientA 38-year-old woman received embryos from IVF by intracytoplasmic sperm injection (ICSI) with her own oocytes that were cryopreserved by slow freezing in a low-sodium medium 14 years and 6 months before, when she was 24 years old.Result(s)From six metaphase-II oocytes thawed, two survived, one was fertilized after ICSI and a cleaving embryo was transferred on day 3. A single term pregnancy was achieved, ending with the delivery of a healthy girl.Conclusion(s)Cryopreservation after slow freezing in a sodium depleted medium maintained the developmental competence of oocytes after long-term storage and resulted in a successful live birth. As far as is known, this case represents, up to date, the longest storage period of cryopreserved human oocytes resulting in a live birth.  相似文献   

5.

Purpose

The purpose of the study is to compare the newborns weight in singleton term birth following transfer of thawed blastocysts–frozen on either day 5 or day 6 after in vitro fertilization.

Method

The retrospective study included 1444 frozen–thawed blastocyst transfer (FBT) cycles resulting in live singleton births between Jan 2013 and Dec 2016. The main outcomes measured were absolute birth weight, z-score adjusted for gestational age and gender, and incidence of large-for-gestational-age (LGA) newborns. Generalized linear model (GLM) and logistic regression were used in multivariate analyses.

Result(s)

Both the absolute birth weight (3416.49?±?404.74 vs 3349.22?±?416.17) and the z-score (0.6?±?0.93 vs 0.41?±?0.93) were significantly higher on day 6 FBT in comparison with day 5 FBT. The incidence of LGA newborns was also increased on day 6 FBT (22.8 vs 14.7%, P?=?0.006). Adjusted for maternal age, BMI, PCOS diagnosis, present of vanishing twin, and embryo quality, the odds ratio (95% confidence interval) for LGA on day 6 FBT comparing with day 5 FBT was 1.76 (1.18–2.64).

Conclusion(s)

Day 6 FBT is associated with increased birth weight and contributes to the incidence of LGA newborns in FBT.
  相似文献   

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Research questionIs there a difference in blastocyst formation between fresh and vitrified–warmed sibling oocytes and can this difference be attributed to changes in embryo morphokinetics?DesignBetween February 2016 and December 2017, 472 metaphase II (MII) oocytes in 67 donor–recipient cycles from 27 different healthy anonymous oocyte donors were allocated for fresh transfer (FSHO) (n = 220) to a synchronous recipient (n = 36) or vitrified (VITO) (n = 252) to be warmed and transferred to another recipient (n = 31). Embryos derived from the FSHO and their sibling VITO were analysed for morphokinetic development using time-lapse imaging, blastocyst formation and clinical outcome.ResultsTime-lapse analysis showed an overall delay in cleavage rate from the time of pronuclei disappearance up to the time of blastulation in the VITO compared with their sibling FSHO. Twelve morphokinetic variables were significantly different between the groups. On Day 5 significantly more FSHO embryos developed to blastocyst (expansion 1–6) and reached the full blastocyst stage (expansion 3–6) compared with the VITO embryos [53.2% (84/158) versus 40.0% (64/160); P = 0.0244 and 48.1% (76/158) versus 31.3% (50/160); P = 0.0028, respectively]. The embryo utilization rate was similar in both groups at the time of cryopreservation; 51.3% (FSHO) versus 45.0% (VITO) (P = 0.3124). The pregnancy rate per cycle was 47.2% (17/36) in FSHO patients and 48.4% (15/31) in VITO patients (P = 1). Limitations in this study: non-randomized, small study size and not powered to detect differences in clinical outcomes.ConclusionsTiming of development is altered and blastocyst formation is delayed in embryos derived from vitrified–warmed donor oocytes compared with their fresh sibling counterparts. Although preliminary results suggest that the clinical impact of this delay may be limited, this needs further investigation in larger randomized studies.  相似文献   

8.
Research questionCan serum kisspeptin levels 14 and 21 days after frozen–thawed embryo transfer predict the early pregnancy outcome of patients?DesignProspective study, with 133 patients undergoing frozen–thawed embryo transfer. Patients were divided into non-pregnant group and pregnant group (including biochemical pregnancy, singleton pregnancy, miscarriage and twin groups).ResultsSerum kisspeptin levels on day 21 were significantly higher than day 14 in singleton pregnancy, miscarriage and twin groups (all P < 0.0001), but not in the biochemical pregnancy group. Similarly, serum human chorionic gonadotrophin (HCG) levels were higher on day 21 compared with day 14 except for the biochemical pregnancy group. Compared with the twin group (296.9 pg/ml), the other four groups showed significantly higher serum kisspeptin levels on day 14 (non-pregnant 548.9, biochemical pregnancy 440.4, miscarriage 434.9, singleton pregnancy group 420.9 pg/ml, P < 0.01, P = 0.016, P = 0.034, P = 0.036, respectively). The miscarriage (762.2 pg/ml), singleton pregnancy (730.8 pg/ml) and twin groups (826.3 pg/ml) had significantly higher kisspeptin levels than the biochemical pregnancy group (397.3 pg/ml) on day 21 (P < 0.001, P < 0.01, P < 0.001, respectively). Serum kisspeptin levels on day 14 were negatively correlated with embryo implantation rate (P = 0.035, R2 = –0.880). Serum kisspeptin levels on day 21 have a poor predictive value of miscarriage compared with serum HCG levels (area under the curve = 0.53 and 0.78, respectively).ConclusionsSerum kisspeptin levels on day 14 are negatively correlated with embryo implantation rate. Serum kisspeptin levels on day 21 have a poor predictive value of miscarriage.  相似文献   

9.
Research questionWhen and how does the gradual transition of the endocrine control of early pregnancy from the corpus luteum to the placenta, termed luteoplacental shift, take place?DesignProspective analysis of serum progesterone levels in pregnancies (n = 88) resulting from programmed frozen–thawed embryo transfer cycles in which ovulation was suppressed and no corpus luteum was present. Dydrogesterone, which does not cross-react with progesterone in immunoassay or spectrometric assay, was used for luteal phase and early pregnancy support. Progesterone, oestradiol and hCG were measured at regular intervals from before pregnancy achievement until +65 to 71 days after embryo transfer by Roche Elecsys electrochemiluminescence immunoassay (Elecsys ECLIA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS).ResultsSerum progesterone remained at baseline levels on first blood analysis +9 to 15 days after embryo transfer and increased only marginally independently from the type of pregnancy up to +16 to 22 days after embryo transfer. From +23 to 29 days after embryo transfer, progesterone increased non-linearly above 1.0 ng/ml and increased further throughout the first trimester with elevated levels in multiples. Oestradiol levels increased in parallel with progesterone; hCG plateaued around +37 to 43 days. Progesterone levels were significant predictors for pregnancy viability from +23 to 29 days after embryo transfer onwards with best accuracy +37 to 43 days after embryo transfer (receiver operator characteristic analysis area under the curve 0.98; 95% CI 0.94 to 1; P = 0.0009).ConclusionsThe onset of substantial progesterone production is the 7th gestational week. Progesterone increase is non-linear, depends on chorionicity and zygosity, and may have predictive potential on the outcome of pregnancies originating from frozen embryo transfer cycles.  相似文献   

10.
Abstract

At present, the precise role of GnRH agonists during the luteal phase remains uncertain. In the present study, a meta-analysis was used to evaluate the effect of administering a GnRH agonist to during the luteal phase in patients undergoing FET cycles. A literature review was carried out by searching the current content of MEDLINE, Embase, the Cochrane Controlled Trials Register and Ovid. We particularly focused upon implantation rate, CPR per transfer, and ongoing pregnancy rate. All of the trials analyzed involved a GnRH agonist administered during the luteal phase. Six trials involving 1137 women were included in our meta-analysis. All of the cycles analyzed exhibited significantly higher implantation rates, clinical pregnancy rates, and ongoing pregnancy rates in the group of patients administered with a GnRH agonist during the luteal phase compared with the control group that did not receive a GnRH agonist during the luteal phase. Our data, therefore, demonstrate that the administration of a GnRH agonist during the luteal phase can significantly increase clinical pregnancy and ongoing pregnancy rates in FET cycles. The implantation rates, clinical pregnancy rates, and ongoing pregnancy rates can significantly increase in the group of patients administered with a GnRH agonist in natural cycle FET.  相似文献   

11.
Spontaneous ovulation during a natural menstrual cycle represents a simple and efficient method for synchronization between frozen embryos and the endometrium. The objective was to compare serial monitoring until documentation of ovulation, with human chorionic gonadotrophin (HCG) triggering, for timing frozen embryo transfer (FET) in natural cycles (NC). In a retrospective study, 112 women with regular menstrual cycles undergoing 132 NC–FET cycles were divided into two groups: group A (n = 61) patients had FET in an NC after ovulation triggering with HCG; group B (n = 71) patients had FET in an NC after spontaneous ovulation was detected. The main outcome measure was the number of monitoring visits at the clinic. Patients in both groups were similar in terms of demographic characteristics and reproductive history. Clinical and laboratory characteristics of fresh and frozen cycles were also found comparable for both groups, as were pregnancy and delivery rates. The number of monitoring visits in group A (3.46 ± 1.8) was significantly lower than in group B (4.35 ± 1.4) (P < 0.0001). In patients undergoing NC–FET, triggering ovulation by HCG can significantly reduce the number of visits necessary for cycle monitoring without an adverse effect on cycle outcome. Ovulation triggering can increase both patient convenience and cycle cost-effectiveness.  相似文献   

12.

Purpose

To evaluate the clinical efficacy of letrozole on ovulation induction and hormone replacement therapy (HRT) during endometrial preparation for frozen–thawed embryo transfer (FET).

Methods

We analyzed totally 1,230 cycles of patients that underwent FET from October 2010 to September 2012. Seven hundred and thirteen cycles of patients with ovulation disorders that underwent FET were randomly assigned to two groups by case control study. 359 cycles received letrozole ovulation induction and 354 cycles received HRT during endometrial preparation for FET, respectively. In the corresponding period, 517 cycles of patients with normal ovulation in the natural cycle group for FET endometrial preparation served as controls. Reproduction-related clinical outcomes of patients in the three groups were compared.

Results

The embryo implantation rate of patients in letrozole group (30.4 %) was significantly higher than the HRT group (22.8 %, P < 0.05). The clinical pregnancy rate of patients in the letrozole group (53.2 %) was significantly higher than the HRT group (44.4 %, P < 0.05), while no significant difference was observed between the letrozole and natural cycle groups (51.3 %, P > 0.05). Estradiol levels on the day of human chorionic gonadotropin administration in the letrozole group were significantly lower than those in the natural cycle group (280.32 ± 125.39 pg/ml and 351.06 ± 123.03 pg/ml, respectively; P < 0.05). The live birth rate of patients in letrozole group (44.6 %) was significantly higher than the HRT group (32.5 %, P < 0.05), while abortion rate (12.0 %) was significantly lower than the HRT group (21.0 %, P < 0.05). There were no significant differences in number of mature follicles, endometrial thickness, duration of follicle growth between the letrozole and the natural cycle groups, and there were no significant differences in twin birth rate and ectopic pregnancy rate among the three groups (all P values >0.05).

Conclusions

Ovulation induction with letrozole during endometrial preparation for FET has a higher rate of pregnancy success and a lower abortion rate than HRT. Letrozole treatment exhibits clinical progression and outcomes similar to those patients undergoing a natural cycle or normal ovulation cycle. Therefore, letrozole treatment may be an effective option in endometrial preparation for FET in patients with ovulation disorders or irregular menstruation.  相似文献   

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14.

Purpose

To investigate the ability of medium conditioned with bovine cumulus–oocyte complexes (COCs) to support nuclear maturation of canine oocytes recovered from domestic dog ovaries.

Methods

Cumulus–oocyte complexes were obtained from ovaries of domestic bitches (8 months old to 7 years old), and in-vitro maturation was evaluated in TCM-199 supplemented with different concentrations (0, 20, 30 or 50%) of bovine COCs-conditioned medium (BCM). The canine COCs were cultured for 72 or 96 h at 38.5°C in 5% CO2, 5% O2 and 90% N2. The bovine COCs-conditioned medium was obtained from culture of bovine COCs with TCM-199 supplemented with 5% FCS for 22 h at 38.5°C in 2% CO2, 98% air.

Results

The proportion of germinal vesicle breakdown (GVBD) after 72 h was significantly higher (P < 0.05) in medium supplemented with 30% BCM (20.7%) compared with the control group (13.4%). The rates of GVBD-MII stage were significantly higher (P < 0.05) when oocytes were matured with BCM at concentration of 30% (41.5%) compared with control (26.6%) after 72 h in-vitro culture. After 96 h in-vitro culture, the oocytes matured in medium supplemented with 30% BCM (5.5%) showed a significant increase (P < 0.05) in the proportion of MII compared with control (0.7%). However, increasing the cultivation time from 72 to 96 h resulted in an increase in oocyte degeneration rate.

Conclusions

The results suggested that bovine COCs-conditioned medium supplementation significantly increased nuclear maturation of canine oocytes.  相似文献   

15.
16.
The study compares outcomes for patients with frozen embryos who had frozen–thawed embryo transfer (FET) timed to their natural ovulation cycle versus cycles in which endometrial timing was programmed with oestrogen and progesterone. A total of 1205 patients undergoing 1677 FET cycles between 1 January 2000 and 31 December 2006 were analysed. Comparisons were made for patients undergoing modified natural versus programmed FET cycles, as well as between patients using their own eggs for frozen embryos versus those using donor-egg-derived embryos. Clinical pregnancy (gestational sac on 7 week ultrasound) rates (CPR), as well as miscarriage rates, were significantly higher in programmed FET cycles in patients using their own eggs (106/262, 40.5% per embryo transfer, P = 0.015) However, there was not a difference in delivered pregnancies between cycle types in own egg patients (natural cycle delivery rate 245/862, 28.4%; programmed cycle delivery rate 77/262, 29.4%). Furthermore, CPR were not different in natural (38/129, 29.5%) versus programmed cycles (144/424, 34.0%) for ovum donor recipients, nor were delivered pregnancy rates different in natural (33/129, 25.6%) versus programmed cycles (114/424, 26.9%) for ovum donor recipients. In conclusion, there is no significant difference in delivery rates for FET in natural (278/991, 28.1%) versus programmed (191/686, 27.8%) cycles using both own embryos and donor-egg-derived embryos.  相似文献   

17.
This systematic review of literature and meta-analysis of observational studies reports on perinatal outcomes after frozen embryo transfer (FET). The aim was to determine whether natural cycle frozen embryo transfer (NC-FET) in singleton pregnancies conceived after IVF decreased the risk of adverse perinatal outcomes compared with artificial cycle frozen embryo transfer (AC-FET). Thirteen cohort studies, including 93,201 cycles, met the inclusion criteria. NC-FET was associated with a lower risk of hypertensive disorders in pregnancy (HDP) (RR 0.61, 95% CI 0.50 to 0.73), preeclampsia (RR 0.47, 95% CI 0.42 to 0.53), large for gestational age (LGA) (RR 0.93, 95% CI 0.90 to 0.96) and macrosomia (RR 0.82, 95% CI 0.69 to 0.97) compared with AC-FET. No significant difference was found in the risk of gestational hypertension and small for gestational age. Secondary outcomes assessed were the risk of preterm birth (RR 0.83, 95% CI 0.79 to 0.88); post-term birth (RR 0.48, 95% CI 0.29 to 0.80); low birth weight (RR 0.84, 95% CI 0.80 to 0.89); caesarean section (RR 0.84, 95% CI 0.77 to 0.91); postpartum haemorrhage (RR 0.39, 95% CI 0.35 to 0.45); placental abruption (RR 0.61, 95% CI 0.38 to 0.98); and placenta accreta (RR 0.18, 95% CI 0.10 to 0.33). All were significantly lower with NC-FET compared with AC-FET. In assessing safety, NC-FET significantly decreased the risk of HDP, preeclampsia, LGA, macrosomia, preterm birth, post-term birth, low birth weight, caesarean section, postpartum haemorrhage, placental abruption and placenta accreta. Further randomized controlled trials addressing the effect of NC-FET and AC-FET on maternal and perinatal outcomes are warranted. Clinicians should carefully monitor pregnancies achieved by FET in artificial cycles prenatally, during labour and postnatally.  相似文献   

18.
Abstract

The aim of this retrospective cohort study was to investigate which preparation method is optimal for frozen–thawed embryo transfer (FET) treatment. Analyses were performed on 3160 FET cycles, including 654 cycles with a natural cycle (NC) protocol and 2506 cycles with an artificial cycle (AC) protocol. The primary outcome measures were the clinical pregnancy rate (CPR) and the live birth rate (LBR) per transfer. The Student’s t-test, chi-square test and multiple logistic regression were used for statistical analysis. The CPR per transfer was 49.4% in the NC group and 58.6% in the AC group (OR?=?1.270, 95% CI: 1.037–1.554). The LBR per transfer was 42.2% and 50.8% in the NC and AC groups, respectively (OR?=?1.269, 95% CI: 1.037–1.552). Dividing the patients according to the type of transferred embryos, the CPR (67.3% versus 57.0%, p?<?0.01) and LBR (58.8% versus 49.7%, p?<?0.01) were higher after the AC protocol than after NC protocol in patients with blastocyst transfer. The NC and AC protocols yielded comparable CPR and LBR in the patients with cleavage embryo transfer. Our data indicate better pregnancy outcomes after the AC protocol than after the NC protocol. The AC protocol should be recommended in patients who were counseled before receiving FET treatment. Further studies are needed to confirm this finding.  相似文献   

19.

Objective

The purpose of this study is to assess the effect of luteal phase supplementation (LPS) on pregnancy rates in human chorionic gonadotropin (hCG)-induced natural frozen–thawed (FET) cycles.

Study design

All performed hCG-induced natural FET cycles from January 2006 until August 2007 were retrospectively identified. The study group consisted of 452 cycles: 243 supplemented with progesterone administration (600 mg natural micronized progesterone in three separate doses) and 209 without progesterone. Analysis was limited to cycles where embryos were cryopreserved on day 3. Final oocyte maturation was achieved by hCG when endometrial thickness of ≥7 mm and a follicle of 17 mm were present on ultrasound.

Results

No statistically significant differences were observed in ongoing pregnancy rate between the two groups (22% versus 21%, p = 0.8; difference +1%; 95% confidence interval (CI): −6.5 to +8.7). The non-significant effect of the presence or not of luteal support on pregnancy rate was confirmed by logistic regression (odds ratio (OR): 0.9, 95% CI: 0.54–1.47, P = 0.64). A previous pregnancy following fresh embryo transfer (OR: 6.04, 95% CI: 3.63–10.02, P = 0.001) and increased endometrial thickness (OR: 1.25, 95% CI: 1.11–1.41, P = 0.001) significantly affected the achievement of ongoing pregnancy, whereas the association between embryo score and achievement of pregnancy was marginally significant (OR:0.28, 95% CI: 0.08–0.97, P = 0.05).

Conclusion

There is no convincing evidence to support the use of LPS in hCG-induced natural FET cycles, since there is no luteal phase defect. Further prospective randomized studies are necessary to confirm these findings.  相似文献   

20.

Purpose

This study is a retrospective collection of aggregated data from all the Italian ART centers reporting to the Italian National Register from cycles started between January 2005 and December 2013.

Methods

Data from both slow freezing (SF) and vitrification (V) were assessed for the period 2007–2013, while during the years 2005–2006 cryopreservation was exclusively performed by SF.

Results

In the study period, a total of 2,526,024 oocytes were retrieved (from 378,543 retrievals), of which 1,346,061 (53.3 %) were inseminated in fresh cycles and 214,481 (8.5 %) were cryopreserved. Cryopreserved oocytes were used in 24,173 cycles yielding 19,453 transfer cycles (80.5 % of the thawing/warming cycles) and 3043 clinical pregnancies (15.6 % per transfer). A significant difference in implantation (8.7 vs 12.9 % OR 1.30 CI 1.20–1.40) and pregnancy rates per transfer (12.2 vs 14.9 % OR 1.34 CI 1.23–1.46) was found between SF and V. Complete outcome data was available for 2708 pregnancies (89.8 %), leading to 1882 deliveries and 2152 live births. Neonatal major congenital anomalies were 0.9 % (20/2152).

Conclusions

A wide variation in pregnancy rates were found among different centers and lower rates were reported in donor cycles and in centers with more experience.
  相似文献   

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