Pregnancy Outcomes for Day 5 Versus Day 6 Single Frozen-thawed Blastocyst Transfer with Different Qualities of Embryos: A Large Matched-cohort Study

Objective This study aimed to determine whether the day of blastocyst expansion affects pregnancy outcomes in frozen-thawed blastocyst transfer(FBT)cycles.Methods A retrospective match-cohort study was conducted.Patients who underwent blastocyst transfer in frozen-thawed cycles at day 5 or 6 were matched for potential confounding factors.A total of 2207 matched pairs of FBT cycles were included from January 2016 to December 2019 in our Reproductive Medicine Center.Results The clinical pregnancy rate(CPR)and live birth rate(LBR)were significantly increased in day 5 blastocyst transfers when compared to day 6 blastocyst transfers,in terms of the same embryo quality.For FBT cycles with good-quality embryo,the CPR at day 5 and 6 was 61.30%and 57.56%,respectively(P=0.045),and the LBR was 44.79%and 36.16%,respectively(P<0.001).For FBT cycles with poor-quality embryo,the CPR at day 5 and 6 was 48.61%and 40.89%,respectively(P=0.006),and the LBR was 31.71%and 25.74%,respectively(P=0.019).The CPR for FBT cycles with good-quality embryo was statistically higher at day 6 than that at day 5 with poor-quality embryo transferred(57.56%vs.48.61%,P=0.001).Maternal age,anti-Müllerian hormone(AMH),endometrial thickness,embryo quality,and the day of blastocyst expansion were independently correlated with the CPR and LBR.The FBT cycles at day 5 had significantly higher CPR(adjusted odds ratio[OR]=1.246,95%confidence intervals[CI]:1.097–1.415,P=0.001)and LBR(adjusted OR=1.435,95%CI:1.258–1.637,P<0.001)than those at day 6.Conclusion The embryo quality is the primary indicator for FBT cycles.Day 5 blastocysts should be preferred when the quality of embryo at day 5 is the same as that at day 6.

Research progress on the effect of oocyte smooth endoplasmic reticulum clusters on early embryo development and pregnancy outcome

With the clinical development and application of intracytoplasmic sperm injection(ICSI)technology in human assisted reproduction,the influence of oocyte quality on embryo development has been paid more and more attention.So far,there have been many reports on oocyte morphology affecting embryo development.It has been found in some works that the appearance of smooth endoplasmic reticulum clusters(SERC)in oocytes may affect the fertilization and embryo development of oocytes.However,with the increasing reports of SERC-containing oocytes obtained by in vitro fertilization and healthy offspring in recent years,there is still some controversy on whether to continue to use SERC-containing oocytes for the following assisted reproductive therapy in clinical practice.Based on this,this review aims to review the research progress of SERC in oocytes in recent years.

Effects of Medicines and Supplements on Spontaneous Pregnancy and Semen Parameters in Male Infertility:A Systematic Review Update and Network Meta-Analysis

In this study,we used a network meta-analysis(NMA)to compare the effectiveness of medicines and supplements for idiopathic male infertility and to identify the best treatment.Medline,Excerpta Medica Database(EMBASE),Ovid,and China National Knowledge Infrastructure(CNKI),were searched for the period from January 1990 to June 2021 using the keywords"male infertility,""medical therapy,""supplement/nutrient therapy,"and related terms.Randomized controlled trials(RCTs)investigating medicines(mainly follicle-stimulating hormone(FSH),androgen,and clomiphene/tamoxifen)or supplements(mainly zinc,selenium,vitamin C or E,carnitine,coenzyme Q10(CoQ10),or combined treatment)for idiopathic infertile men were selected for meta-analysis.Preferred reporting items for systematic reviews and meta-analysis(PRISMA)was used for data extraction,and a risk-of-bias tool and grades of recommendation,assessment,development,and evaluation(GRADE)system adapted to the NMA were employed to assess the quality of the evidence.The primary outcomes were live birth and spontaneous pregnancy rate(SPR).The secondary outcomes were sperm parameters(including concentration,progressive motility,and morphology)and side effects.In total,65 RCTs involving 7541 men with sperm abnormalities but normal hormone levels were included.A total of 36 studies reported SPR but only three reported live birth rates.The quality of the included studies was found to be moderate to high.Compared with a placebo or being untreated,carnitine plus vitamins significantly improved SPR(relative risk(RR)=3.7,95%confidence interval(95%CI),1.6-8.5);fatty acids significantly increased sperm concentrations(mean difference(MD)=12.5×10^(6)mL-1,95%CI,3.1×10^(6)-22.0×10^(6));and selective estrogen receptor modulator(SERM)plus CoQ10 significantly improved sperm progressive motility(MD=11.0%,95%CI,0.1%-21.9%)and normal sperm morphology(MD=11.0%,95%CI,4.6%-17.4%).The most optimal intervention was carnitine plus vitamins and fatty acids for SPR and sperm concentrations,respectively,even after excluding trials at a high risk of bias.Compared with a placebo or being untreated,FSH(RR=4.9,95%CI,1.1-21.3)significantly increased SPR,whereas SERM plus kallikrein increased sperm concentration(MD=16.5×10^(6)mL^(-1),95%CI,1.6×10^(6)-31.4×10^(6)),and SERM plus CoQ10 significantly improved sperm progressive motility(MD=11.3%,95%CI,7.3%-15.4%)and normal morphology(MD=11.2%,95%CI,5.4%-16.9%)in men with oligoasthenozoospermia(OA).In terms of side effects,fatty acids and pentoxifylline were associated with foul breath and/or a bad taste(RR=8.1,95%CI,1.0-63.5)and vomiting(RR=8.0,95%CI,1.0-63.0),respectively.In conclusion,the optimal treatment for male infertility for live birth is still unknown.Carnitine plus vitamins and FSH are likely to be better than other therapies in achieving successful spontaneous pregnancy in couples overall and in cou ples with men with OA,respectively.The efficacy of other treatments on pregnancy outcomes warrants further verification.

Analysis of Factors Influencing Pregnancy Rate in Frozenthawed Embryo Transfer

Objective To analyse factors influencing the outcome of frozen-thawed embryo transfer （FET）. Method A retrospective analysis was performed in our center on 129 thawing cycles from March 2001 to April 2003. The related parameters were compared between conceived and non-conceived cycles. Results There were totally 129 clinical pregnancies in these transfers （pregnancy rate： 27.1%）. Frozen-thawed embryos were transferred to natural cycles and CC cycling and hormone replacement treatment had equal success. Groups of IVF and ICSI did not differ significantly in pregnancy rates （P〉0.05）. The pregnancy rates for one, two, three and four pre-embryos transfer were 0, 20.0%,44.1% and 75.0%, respectively （P〈0.05）. There were statistical differences between pregnancy group or non- pregnancy group in the endometrial thickness, CES, CES/No. of embryo. A higher pregnancy rate was observed in embryo transfers which had at least one 4-cell grade I embryo （d 2）（P〈0.01）. Conclusions The most important factors influencing the implantation rate and pregnancy rate of frozen-thawed embryo transfer are age, endometrium thickness, and the number, morphology and growth rate of transferred frozen embryos of women participants.

Pregnancy Rate after Embryo Transfer on Day 5 and Day 6 in IVF. A Systematic Review and Meta-Analysis

Study Question: The question: is there any difference in pregnancy rate between embryo transfer day 5 and day 6 in IVF? What Is Known Already? Blastocyst transfer is increasingly popular in assisted reproductive technology (ART) centers today. Very few articles concentrate on comparing Day 5 and Day 6 embryo transfer with conflict results. Objective, Study Design: Systematic review and meta-analysis of published controlled studies. Searches conducted from 2001-2020 on PubMed. Medline, EMBASE, and ISI Web of Science Electronic database is used to collect data, using the following search terms: blastocyst, Day 5, Day 6, embryo transfer (E.T.) and pregnancy rate. Materials, Setting, Methods: A total of 6 full-text articles preselected from 211 references, based on title and abstract. Two independent reviewers performed data selection and extraction according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement (PRISMA). This systematic review was conducted according to (PICO) standard. Random-effect meta-analysis performed on all data (overall analysis). Results and the Role of Chance: Data from 6 relevant articles were extracted and integrated into the meta-analysis that reported clinical pregnancy rate (CPR) as an outcome in 5640 cycles, 2274 cycle had embryo transfer at day 6 and the control was 3366 cycle had embryo transfer day 5 showed a significantly higher clinical pregnancy rate following Day 5 embryo transfer compared with Day 6 embryo transfer with odd ratio and 95% confidence limit 0.73 (0.66 - 0.82) p value < 0.000. Sensitivity analysis led to similar results and conclusions. Limitations, Reasons for Caution: The validity of meta-analysis results depends mainly on the quality and the number of published studies available. Indeed, this meta-analysis included no randomized controlled trial (RCT). Wider Implications of the Findings: In regards to the results of this original meta-analysis, ART practitioners should preferably transfer D5 rather than D6 blastocysts. Further RCTs are needed to address the question of whether D6 embryos should be transported.

Effect of autologous bone marrow stem cells-scaffold transplantation on the ongoing pregnancy rate in intrauterine adhesion women:a randomized,controlled trial

Intrauterine adhesion is a major cause of female reproductive disorders.Although we and others uncontrolled pilot studies showed that treatment with autologous bone marrow stem cells made a few patients with severe intrauterine adhesion obtain live birth,no large sample randomized controlled studies on this therapeutic strategy in such patients have been reported so far.To verify if the therapy of autologous bone marrow stem cells-scaffold is superior to traditional treatment in moderate to severe intrauterine adhesion patients in increasing their ongoing pregnancy rate,we conducted this randomized controlled clinical trial.Totally 195 participants with moderate to severe intrauterine adhesion were screened and 152 of them were randomly assigned in a 1:1 ratio to either group with autologous bone marrow stem cells-scaffold plus Foley balloon catheter or group with only Foley balloon catheter(control group)from February 2016 to January 2020.The per-protocol analysis included 140 participants:72 in bone marrow stem cells-scaffold group and 68 in control group.The ongoing pregnancy occurred in 45/72(62.5%)participants in the bone marrow stem cells-scaffold group which was significantly higher than that in the control group(28/68,41.2%)(RR=1.52,95%CI 1.08–2.12,P=0.012).The situation was similar in live birth rate(bone marrow stem cells-scaffold group 56.9%(41/72)vs.control group 38.2%(26/68),RR=1.49,95%CI 1.04–2.14,P=0.027).Compared with control group,participants in bone marrow stem cells-scaffold group showed more menstrual blood volume in the 3rd and 6th cycles and maximal endometrial thickness in the 6th cycle after hysteroscopic adhesiolysis.The incidence of mild placenta accrete was increased in bone marrow stem cells-scaffold group and no severe adverse effects were observed.In conclusion,transplantation of bone marrow stem cells-scaffold into uterine cavities of the participants with moderate to severe intrauterine adhesion increased their ongoing pregnancy and live birth rates,and this therapy was relatively safe.

Effect of flaxseed supplementation on metabolic state,endocrine profiles,body composition and reproductive performance of sows

Objective:To assess the effect of flaxseed supplementation on metabolic profile,endocrine concentrations,non-esterified fatty acids(NEFA),body composition variables,and reproductive performance of sows.Methods:All the 21 crossbred Large White Yorkshire sows were considered in the study period starting at day 1 of current farrowing when the feeding of specific supplemental ration was started until the day of subsequent farrowing(days 150-155)and were equally allocated into three groups.Group 1 served as the control group and followed their normal feeding schedule.Group 2 and group 3,in addition to their normal feeding schedule,were supplemented with flaxseed at a rate of 0.5%and 1.0%of the dry matter,respectively.Blood samples were collected 15 days prior to farrowing,on the day of farrowing(day 0),at weekly intervals until day 28 of lactation and at monthly intervals during gestation to harvest the plasma.Plasma was used to assess the metabolic and endocrine status of sows.Body weight of each sow and individual birth weight of all piglets born were measured.Results:Flaxseed supplementation led to decrease in plasma cholesterol and triglyceride levels in the supplemented groups than in the control group(P<0.05).Plasma estradiol-17βlevel was higher in group 2 than that in group 1 and 3 on day 90 of the gestation period(P<0.05).The mean plasma level of insulin-like growth factor 1 was higher in group 3 than that in group 1 and 2 both in late lactation(day 28)as well as in early gestation(day 30)(P<0.05).Plasma NEFA and weight gain were greater in sows of group 2 and 3 compared to those fed with the normal control diets(P<0.05).The proportion of pregnant sows relative to sows bred was 100.0%in group 2 and 3 and 85.7%in the control group.Piglet mortality was lower in group 2 and 3 compared to group 1(P>0.05).Conclusions:Flaxseed improves endocrine profiles,NEFA concentrations and body weight,resulting in better pregnancy rate and litter size.

Oncology and reproductive outcomes over 16 years of malignant ovarian germ cell tumors treated by fertility sparing surgery

BACKGROUND Malignant ovarian germ cell tumors(MOGCT)are rare and frequently occur in women of young and reproductive age and the oncologic and reproductive outcomes after fertility-sparing surgery(FSS)for this disease are still limited.AIM To evaluate the oncology and reproductive outcomes of MOGCT patients who underwent FSS.METHODS All MOGCT patients who underwent FSS defined as the operation with a preserved uterus and at least one side of the ovary at our institute between January 2005 and December 2020 were retrospectively reviewed.RESULTS Sixty-two patients were recruited for this study.The median age was 22 years old and over 77%were nulliparous.The three most common histology findings were immature teratoma(32.2%),dysgerminoma(24.2%),and yolk sac tumor(24.2%).The distribution of stage was as follows;Stage I,74.8%;stage II,9.7%;stage III,11.3%;and stage IV,4.8%.Forty-three(67.7%)patients received adjuvant chemotherapy.With a median follow-up time of 96.3 mo,the 10-year progressionfree survival and overall survival were 82.4%and 91%,respectively.For reproductive outcomes,of 43 patients who received adjuvant chemotherapy,18(41.9%)had normal menstruation,and 17(39.5%)resumed menstruation with a median time of 4 mo.Of about 14 patients who desired to conceive,four were pregnant and delivered good outcomes.Only one case was aborted.Therefore,the successful pregnancy rate was 28.6%CONCLUSION The oncology and reproductive outcomes of MOGCT treated by FSS are excellent.Many patients show a long survival time with normal menstruation.However,the obstetric outcome is not quite satisfactory.

Can apoptosis analysis of cumulus granulosal cell evaluatethe potential vitality of replaced embryo?

Objective: We evaluated the relationships between the incidence of the apoptotic cell of human granulose cell (GC) from the oocytes during intracytoplasmic sperm injection (ICSI) and the pregnancy rate. Methods: 275 oocytes were retrieved from 29 patients with aging between 23 - 38 years, who underwent ICSI (21), percutanious sperm aspiration (PESA-ICSI)and testicular sperm extraction (TESE-ICSI) (7), only one case came from conventional IVF. The patients were divided into two groups based on pregnancy or not. The cumulus cells were collected to measure the number of apoptotic cell by using flow cytometer. The degree of cumulus GC apoptosis and clinic pregnancy rate were assessed, and compared with embryo morphology and number of blastomere. Results: The apoptosis value in pregnancy gruop (9 cases) were lower than the nonpregnancy group (19 cases) (P<0. 05). In pregnancy group, the apoptosis value in the GC obtained from replaced embryos (37) were significantly lower than that of the nonreplaced embryos (78) (P<0. 02). Conclusion: The results indicated that the embryos with lower apoptosis value would have the potency of increase pregnancy rate. It will be possible to elevate the clinic pregnancy rate by selecting the replaced embryos bases on the apoptosis value of GC from oocytes in addition to the morphological score.

Effect of Adding a Delayed Blastocyst to a Good Quality One during Embryo Transfer on ICSI Cycle Outcomes

Objectives: Study the effect of adding a delayed blastocyst to a transferred good quality one on ICSI cycle outcomes. Study design: Prospective cohort study. Participants/materials, setting, methods: 90 infertile patients aged from 20 - 35 years due to mild male factor, unexplained infertility or tubal factor. Patients with PCOS, endometriosis, RIF, poor responder and azoospermia were excluded. Setting: Duration 6 months from October 2019 to April 2020 in a private IVF center in Egypt. 30 cases were subjected to elective single embryo transfer and the other 60 with two embryo transfers, one good quality and another poor quality blastocyst. Results: (clinical pregnancy rate) was comparable between the two groups, being 47.7% and 36.7% in SET and DET groups respectively (p = 0.361). Miscarriage and ectopic pregnancy rate were observed in 10% of the cases pregnant after SET (group I) and in only 6.7% of the cases pregnant after DET (group II) denoting no significant statistical difference between the two groups. The highest incidence was missed miscarriages in the two groups and ectopic pregnancy was observed only in one case in group II (DET). Twin pregnancy occurred in 22% of pregnant females in the second group. Late pregnancy complications in the form of preterm labour, premature rupture of membrane and preeclampsia occurred mainly in pregnant females in the second group 18%. Conclusion: Neither adding a delayed blastocyst negatively affected the good one nor affected the live birth rate but increased multiple pregnancy rates.

Oocyte vitrification:A local validation of the method

Is there a really need to validate oocyte vitrification technique in an ART laboratory before establishing it in daily practice? Validation of micromanipulationbased technique, in this case oocyte vitrification, is essential prior to enlarging its use to routine practice. Oocyte vitrification is a new worldwide used technique and legal recently inFrance. This micromanipulation needs to be performed by a skilled and experienced embryologist and requires an internal assessment in each ART unit before any wide use. We designed a prospective study, from September 2011 to July 2012, using sibling oocytes from women who recovered more than 12 Metaphase II oocytes. A part of freshly recovered oocytes underwent immediate ICSI while the remaining oocytes were vitrified. 87 couples undergoing ICSI were selected based on number of mature oocytes available on the recovery day after denudation. A part of fresh MII oocytes were microinjected and the others were vitrified using an open system (Cryotop?). The major criterion of interest was the number of embryo transferred/ number of Metaphase II ratio for after ICSI on fresh oocytes (42/211) versus vitrified/warmed oocytes (51/204) (p > 0.05). Secondary studied criteria were survival rate (80.5% ± 26.3%), fertilization rate (68.9 ± 33.5) and finally, cumulative pregnancy rate obtained in this study is 40.2%. One of the benefits of such practice is the limitation of embryo freezing. However, the study design delays oocytes warming cycles, due to pregnancies triggered by the transfer of fresh derived oocyte embryos and to the priority to transfer all the frozen embryos before starting oocytes warming. Moreover, no data is available about children’ health. Oocyte vitrification represents not only a change in our daily practice to improve cumulative pregnancy rate but also a promising tool to develop egg banking and donation. Clinical Trials Registration number: 209 R02.

Pregnancy outcomes of four different cycle protocols for frozen embryo transfer: a large retrospective cohort study

Objective:To evaluate the pregnancy outcomes of the four endometrial preparation protocols for people undergoing frozen-thawed embryo transfer(FET),including natural cycle(NC),hormone replacement therapy cycle(HRT),gonadotropin-releasing hormone agonist artificial cycle(GAC),and ovarian stimulation cycle(OC).Methods:This retrospective cohort study enrolled 10,333 cycles of frozen embryo transfer performed at Xinan Gynecological Hospital in Sichuan,China,from January 2018 to December 2018.The patient's baseline characteristics and pregnancy outcomes were extracted from the medical record system.Pregnancy outcomes were compared among the four groups and multiple logistic regression models were used to adjust for the confounding factors.Results:After adjusting for covariates,multiple logistic regression analysis showed no statistical significance in pregnancy outcomes in the HRT group,GAC group,and OC group compared to the NC group in the entire population.The adjusted odds ratio of live birth was 0.976(95%)confidence interval[Cl](0.837-1.138)for the HRT group,0.959(95%confidence interval 0.797-1.152)for the GAC group,and 0.909(95%confidence interval 0.763-1.083)for the OC group.Conclusions:The natural protocol had comparable pregnancy outcomes compared to the other three endometrial preparation protocols in the overall FET population.More high-quality prospective randomized controlled trials are required to assess the efficacy of the four protocols and explore the optimal one.

Intrauterine Insemination—Our Results between the Years 2008-2012

The purpose of this retrospective study was to determine whether or not there was a significant relationship between women’s age as a cause of sterility and pregnancy after IUI. Furthermore, we evaluated the effect of stimulation of antiestrogens and time of hCG administration on the success of IUI in relation to the age of women. During the period between 2008 and 2012, we performed a total number of 793 IUI. Patients were prepared for IUI in the natural cycle and stimulation with antiestrogens (clomiphene citrate-CC). Ovulation was induced by hCG (Ovitrelle) 40 hours before IUI or immediately after the procedure. Sperm was processed through density gradients. The average success rate of IUI was 10.2% of pregnant women per cycle. Significantly the highest number of pregnant women 16.3% was women with a diagnosis of anovulation. Significantly the lowest success rate of IUI was at the immunological cause of infertility and endometriosis. There was no evidence of age dependence for women on the success of IUI. Stimulation of CC did not significantly increase the chance of becoming pregnant. There was also no statistically significant difference in hCG before and after IUI pregnancy success. The most important group of women for whom IUI is a suitable form of assisted reproduction consists of patients of 35 years old with anovulation cause of sterility. Those patients with an immunological cause of infertility and endometriosis have significantly lower chances of conceiving after IUI and it is preferable for them to choose other techniques of assisted reproduction and embryo transfer.

针灸辅助改善冻融胚胎移植疗效的网状meta分析

Objective:To evaluate the clinical effect of acupuncture-moxibustion as the adjuvant therapy on frozenthawed embryo transfer(FET)using network meta-analysis.Methods:In PubMed,Embase,Cochrane Library,Chinese National Knowledge Infrastructure(CNKI),Wanfang database(WanFang),VIP database and Chinese Biomedical Literature Database(SinoMed),the randomized controlled trials(RCTs)of the adjuvant therapy of acupuncture-moxibustion for FET were retrieved,from database inception to April 1,2021.Cochrane risk of bias assessment tool was used to screen and evaluate the quality of the included studies,and RevMan 5.3,GeMTC0.14.3 and Stata16.0 software were adopted to complete the network meta-analysis.Results:Twenty-nine RCTs comprising 2880 patients were finally included,involving 17 interventions and 4 outcome measures.The results of network meta-analysis showed that the top three therapies under each outcome based on the magnitude of SUCRA values were:(1)Clinical pregnancy rate(CPR,%):"transcutaneous electrical acupoint stimulation+herbal medicine"(76.4),"moxibustion+herbal medicine"(74.7),"acupuncture+moxibustion"(73.3);(2)Biochemical pregnancy rate(BPR):"moxibustion+herbal medicine"(89.3),"acupuncture+moxibustion"(82.1),"acupuncture+herbal medicine"(78.7);(3)Endometrial thickness:"acupoint injection+Western medicine"(87.2),auricular therapy(76.8),"acupuncture+herbal medicine"(73.5);(4)Type A endometrial morphology rate:"acupoint injection+Western medicine"(78.3),"moxibustion+herbal medicine"(58.0)and"acupuncture+moxibustion"(52.6).Conclusion:The combined treatment of acupuncture-moxibustion was superior to single therapy for FET patients.The combined therapy of transcutaneous electrical acupoint stimulation and herbal medicine had the best effect for improving CPR,"moxibustion+herbal medicine"obtained the best average comprehensive effect,and"acupoint injection+Western medicine"was conductive to ameliorate the endome trial thickness and morphology.Due to the limitations of existing studies,more high-quality RCTs are needed in the future to further verify these conclusions.

Improving the health and treatment success rates of in vitro fertilization patients with traditional Chinese medicine:Need for more robust evidence and innovative approaches

Maximising access to and the success of fertility treatments should be a priority for global reproductive health,as should overall patient well-being.The demand for in vitro fertilization(IVF)and other assisted fertility treatments has increased over the past decade and is likely to further increase in years to come.Nevertheless,there is still considerable unmet demand for infertility support worldwide.Moreover,the high emotional,physical and financial burden experienced by individuals undergoing IVF cycles can be a risk for their mental and physical health,which in turn can influence treatment continuation and the likelihood of IVF success.Studies from various parts of the world show that most individuals undergoing IVF also use adjunct alternative medicines and procedures,the most common being traditional Chinese medicine(TCM).The complementary and synergistic role of TCM for individuals undergoing IVF is an area that merits further attention and research,both for its potential positive effects on IVF success rates and for its broader physical and mental health benefits.However,much of the existing evidence is not sufficiently robust or consistent for findings to be adopted with confidence.This commentary argues that much work must be done to understand the efficacy and clinical best practices for these integrated approaches.This can be achieved in part by developing more robust and clinically relevant randomized controlled trial protocols,collecting and triangulating evidence through a variety of study designs and methods,and strengthening the collection and pooling of clinic-level data.

Endometriosis Fertility Index for Predicting Pregnancy after Endometriosis Surgery

Background： The endometriosis fertility index （EFI） has a predictive value for pregnancy after surgery. In vitro fertilization and embryo transfer （IVF-ET） is a good treatment to infertility. This study aimed to provide external validation of EFI, assess the factors affecting the ability of EFI to predict cumulative spontaneous pregnancy rates （PRs）, and propose reasonable advice for treatment by evaluating the effect of infertility management combining surgery and IVF-ET. Methods： This retrospective study enrolled 345 endometriosis-related infertile women after laparoscopic surgery from January 2012 to January 2016. Among them, 234 patients tried to conceive naturally and were divided into six groups according to their different EFI scores. Of the 345 patients, 307 with an EFI score 〉5 were divided into non-IVF-ET group （n = 209） and IVE-ET group （n = 98） to compare the cumulative PRs. Cumulative PRs＇ curves were calculated using the Kaplan-Meier product limit estimate and the differences were evaluated by log-rank test. Independent predictive factors for pregnancy were assessed using the Cox regression model. Results： Significant differences in spontaneous PRs among different EFI scores were identified （χ2 = 29.945, P 〈 0.05）. The least function score was proved to be the most important factor for EFI （χ2 = 6.931, P 〈 0.05） staging system. In patients with an EFI score ≥5 after 12 months from surgery, the cumulative PRs of those who received both surgery and IVF-ET were much higher than the spontaneous PRs of those who received surgery alone （χ2 =4.160, P = 0.041）. Conclusions： The EFI is a reliable staging system to predict the spontaneous PR of patients. The least function score was the most influential factor to predict the spontaneous PR. Patients with an EFI score ≥5 after 12 months from surgery are recommended to receive IVF-ET to achieve a higher PR.

Chinese Medicine Sequential Therapy Improves Pregnancy Outcomes after Surgery for Endometriosis-Associated Infertility: A Multicenter Randomized Double-blind Placebo Parallel Controlled Clinical Trial

Objective:To evaluate the efficacy and safety of Chinese medicine(CM)improving pregnancy outcomes after surgery for endometriosis-associated infertility.Methods:A multicenter,randomized,doubleblind placebo parallel controlled clinical trial was designed.A total of 202 patients who had laparoscopy for endometriosis-associated infertility with qi stagnation and blood stasis syndrome were included and randomly divided into the CM treatment group and placebo control group at a ratio of 1:1 using a central block randomization from May 2014 to September 2017,101 patients in each group.The two groups received continuous intervention at 1–5 days after surgery,for 6 menstrual cycles.Before ovulation,the CM group was treated Huoxue Xiaoyi Granule(活血消异颗粒);after ovulation,Bushen Zhuyun Granule(补肾助孕颗粒)was involved.The control group was treated with placebo.Transvaginal ultrasonography was performed every menstrual cycle during the treatment,and female hormone levels in the follicular and luteal phases were measured during the 1 st,3 rd and 6 th menstrual cycles.The analysis was continued until pregnancy.The primary outcomes were clinical pregnancy rate and pregnancy outcome,and the secondary outcomes were follicular development and endometrial receptivity.Safety evaluations were performed before and after treatment.Results:(1)Clinical pregnancy and live birth rates:the clinical pregnancy and live birth rates of the CM group were significantly higher than those of the placebo group[44.6%(45/101)vs.29.7%(30/101),34.7%(35/101)vs.20.8%(21/101),both P<0.05].(2)Follicle development:the incidence of dominant follicles,rate of cumulative cycle ovulation,and rate of cumulative cycle mature follicle ovulation were significantly higher in the CM group than those in the placebo group[93.8%(350/373)vs.89.5%(341/381),80.4%(275/342)vs.69.1%(253/366),65.8%(181/275)vs 56.1%(142/253),P<0.05 or P<0.01]).The incidence of cumulative cycle luteinized unruptured follicle syndrome was significantly lower in the CM group than in the placebo group[11.7%(40/342)vs.17.8%(65/366),P<0.05).(3)Endometrial receptivity:after treatment,both endometrial types and endometrial blood flow types in the CM group were mainly types A and B,while those in the placebo group were mainly types B and C,with a significant difference between the two groups(both P<0.05).(4)Adverse events:the incidence of adverse events between the two groups was not significantly different(P>0.05).Conclusion:Strategies for activating blood circulation-regulating Gan(Liver)-tonifying Shen(Kidney)sequential therapy can effectively improve the clinical pregnancy rate and live birth rate of endometriosis-associated infertility with qi stagnation and blood stasis after laparoscopy,improve follicular development,promote ovulation,improve endometrial receptivity,while being a safe treatment option.(Trial registration No.NCT02676713).

Pregnancy Outcomes of In Vitro Fertilization with or without Ovarian Hyperstimulation Syndrome： A Retrospective Cohort Study in Chinese Patients

Background： The effect of ovarian hyperstimulation syndrome （OH SS） on pregnancy outcomes of in vitro fertilization （IVF） patients is still ambiguous. Tbis study aimed to analyze pregnancy outcomes of IVF with or without OHSS in Chinese patients. Methods： A retrospective cohort study was undertaken to compare pregnancy outcomes between 190 women with OHSS and 197 women without OHSS. We examined the rates of clinical pregnancy, multiple pregnancies, miscarriage, live birth, preterm deliver）,, preterm birth before 34 weeks＇ gestation, cesarean delivery, low birth weight （LBW）, and small-for-gestational age （SGA） between the two groups. Odds ratios （ORs） and 95% confidence intervals （Cls） of measure of clinical pregnancy were also analyzed. Results： The clinical pregnancy rate of OHSS patients was significantly higher than that of non-OHSS patients （91.8% vs. 43.5%, P 〈 0.001）. After controlling for drug protocol and causes of infertility, the adjusted ORs of moderate OHSS and severe/critical OHSS for clinical pregnancy were 4.65 （95% CI, 1.86-11.61 ） and 5.83 （95% CI, 3.45-9.86）, respectively. There were no significant differences in rates of muhiple pregnancy （4.0% vs. 3.7%） and miscarriage （16.1% vs. 17.5%） between the two groups. With regard to ongoing clinical pregnancy, we also found no significant differences in the rates of live birth （82.1% vs. 78.8%）, preterm delivery （20.9% vs. 17.5%）, preterm birth before 34 weeks＇ gestation （8.6% vs. 7.9%）, cesarean delivery （84.9% vs. 66.3%）, LBW （30.2% vs. 23.5%）, and SGA （21.9% vs. 17.6%） between the two groups. Conclusion： OHSS, which occurs in the luteal phase or early pregnancy in IVF patients and represents abnormal transient hemodynamics, does not exert any obviously adverse effect on the subsequent pregnancy.

Effect of Patient Age and Embryo Parameters on Pregnancy Outcomein In Vitro Fertilization-Embryo Transfer(IVF-ET)

Objective To study the effect of patient age, the number and quality of embryos transferred on pregnancy outcome in in vitro fertilization-embryo transfer procedures （IVF-ETs）. Methods A retrospective study was conducted with infertile women who underwent a total of 1 800 cycles of lVF-ET and intracytoplasmic sperm injection （ICSI） at the Reproductive Medicine Center of the Third Affiliated Hospital of Guangzhou Medical College from Jan. 2006 to Dec. 2007. The patients were divided into three groups based on age （year）. 〈30, 30-34 and 235. The rates of clinical pregnancy and multiple pregnancies were compared in each group when 1-3 embryos and 0-3 goodquality embryos were transferred respectively. Results 1） In the group of patients aged 〈30 years, there was no significant difference in pregnancy outcomes with 1-3 embryos transferred. However, pregnancy rates were similar when 2 3 good-quality embryos were transferred, which was significantly higher compared with 0-1 good-quality embryos transferred; the incidence of multiple pregnancies was not an issue when only 1 embryo was transferred. 2） The pregnancy rate of the patients aged 30 34 was not significant not only when only 2-3 embryos were transferred but also when 2-3 good-quality embryos were transferred, which was significant compared with when 1 embryo or 0 1 good-quality embryo was transferred. The subgroup of 3 good-quality embryos transferred, at the same time, was expected to significantly increase multiple pregnancy rate. 3） For the patients aged 235, there were similar pregnancy rates in the subgroup involving 1-3 embryos transferred. Compared with 0-2 good-quality embryos transferred, the pregnancy rate was significantly higher in the patients with 3 good-quality embryos transferred. An increased trend toward multiple pregnancies was observed among not only the subgroups with 1-3 embryos transferred, but also when 1-3 good-quality embryos were transferred, although it was significantly higher in patients with 3 good-quality embryo transferred. Conclusion In an effort to achieve the ideal pregnancy rate without the risk of multiple pregnancies, it is desirable to employ a single good-quality embryo transfer for patients aged 〈30 years and 2 good-quality embryos for patients aged 330. As older women （aged 335 years）, this is important, need to abstain from poor-quality embryo transferred by increasing the number of embryos transferred in an effort to improve the rate of clinical pregnancy, if the patients have had enough 2 high-quality embryos.

Acceleration of coasting enhances pregnancy rate in ICSI cycles at risk for ovarian hyperstimulation syndrome

Objective To assess the efficacy of adding Gn-releasing hormone antagonist（GnR HA） on the day of hC G triggering in a long luteal protocol without withholding the agonist in women who are at a risk to develop ovarian hyperstimulation syndrome（OHSS）.Methods This was a retrospective cohort study conducted upon 50 women who have elevated serum estradiol（E2） level 〉4 500 ng/L at the day of ovum triggering with hC G on a long agonist luteal protocol of controlled ovarian stimulation（COS）. When an exaggerated ovarian response was observed around day 10 of stimulation, immediately the next morning at 6 a.m. gonadotropin administration was stopped or reduced, and a single dose of ganirelix acetate（antagonist） was given sc continuation of the agonist dose hC G. Another serum E2 measurement was done at 6 p.m.（after 12 h of antagonist） then hC G, sc 250 mg and choriogonadotropin α were administered 14 h later after antagonist and documented the reduction of E2 level. Oocyte retrieval was conducted after 34-36 h of hC G administration. The measured outcomes were the level of E2 on the day of hC G injection, number of oocytes and their quality, pregnancy rate and the occurrence of OHSS and its grade in case it happened.Results The total dose for recombinant FSH was 25.3±6.4 ampoules（75 IU/ampoule） while it was 11.0±3.0 ampoules for the urinary hM G. A higher oocyte maturation rate（82.8%） and a high fertilization rate（87.8%） were observed. The mean endometrial thickness was 10.1±1.0 mm on the day of hC G triggering. The higher fertilization rate with the good endometrial thickness observed resulting in a higher pregnancy rate（78.0%, 39/50） with statistically significant（P〈0.05）. A significant reduction of E2 level was documented by a percentage around 40% before hC Ginjection. There were no reported cases of severe or moderate OHSS, however 13 cases（26%） were reported to have mild OHSS constituting.Conclusion Acceleration of coasting in cases of OHSS through treatment with GnR HA after pituitary suppression with GnR H agonist（GnR H-a） offered a novel approach to decrease E2 level, avoided cycle cancellation, and maintain excellent oocyte maturation rate, and finally result in high pregnancy rate with prevention of OHSS.