傳統以為PCO病患服用pill可提高試管懷孕率
本篇指出服用pill反而降低試管活產率  尤其是使用GnRH antagonist療程之病患

Arch Gynecol Obstet. 2019 Sep;300(3):737-750. doi: 10.1007/s00404-019-05210-z. Epub 2019 Jun 6.

Effect of pretreatment with combined oral contraceptives on outcomes of assisted reproductive technology for women with polycystic ovary syndrome: a meta-analysis.

OBJECTIVE:

To evaluate the effect of pretreatment with combined oral contraceptives (COC) on outcomes in women with polycystic ovary syndrome (PCOS) who underwent assisted reproductive technology for subfertility.

METHODS:

Two authors independently searched MEDLINE, EMBASE, and the Cochran Library to identify and review articles published from October 1995 until December 2018 according to selection criteria. Outcomes are expressed as mean difference and odds ratio (OR) in a meta-analysis model.

RESULTS:

A total of seven studies were included in this meta-analysis: one randomized controlled study and two prospective and four retrospective cohort studies. Meta-analysis showed that the COC pretreatment did not affect rate of clinical pregnancy (OR = 0.93, 95% confidence interval CI 0.65-1.34, I2 = 76%) or ovarian hyperstimulation syndrome (OR = 0.90, 95% CI 0.57-1.44, I2 = 0%). However, the rate of miscarriage in the COC group was significantly higher (OR = 1.33, 95% CI 1.02-1.72, I2 = 9%) and the rate of cumulative live birth was significantly lower compared with the control group (OR = 0.72, 95% CI 0.54-0.98, I2 = 55%). Subgroup analysis showed higher rates of miscarriage and lower rates of cumulative live birth in studies with a gonadotropin-releasing hormone (GnRH) antagonist protocol (OR = 1.69, 95% CI 1.17-2.44, I2 = 0% and OR = 0.38, 95% CI 0.29-0.50, respectively).

CONCLUSION:

Pretreatment with COC in women with PCOS before assisted reproductive technology may have an adverse effect on clinical outcomes, especially with a GnRH antagonist protocol.

Day 5形成的囊胚67.7%染色體是正常  著床率: 68.9%
Day  6形成的囊胚52.1%染色體是正常  著床率: 66.8%
Day  7形成的囊胚43.1%染色體是正常  著床率: 52.6%

Hum Reprod. 2019 Sep 29;34(9):1632-1639. doi: 10.1093/humrep/dez138.

Worth the wait? Day 7 blastocysts have lower euploidy rates but similar sustained implantation rates as Day 5 and Day 6 blastocysts.

Abstract

STUDY QUESTION:

Does the reproductive potential of embryos change when blastocyst development takes longer than the traditionally accepted 5 days when accounting for aneuploidy and endometrial-embryo asynchrony?

SUMMARY ANSWER:

Aneuploidy increases with increasing duration of blastulation, but if blastocyst morphologic quality and endometrial-embryo asynchrony are controlled for, euploid Day 7 embryos have similar sustained implantation as compared to Days 5 and 6 euploid blastocysts.

WHAT IS KNOWN ALREADY:

The relative contributions of diminished embryo quality versus endometrial and embryo asynchrony to poor outcomes associated with embryos cultured past Day 6 are not clear. Asynchrony can be eliminated by embryo vitrification with transfer in a subsequent month after retrieval.

STUDY DESIGN, SIZE, DURATION:

Retrospective cohort study of patients from a single center attempting conception through ICSI and utilizing preimplantation genetic testing for aneuploidy screening (PGT-A) from January 2017 to September 2018. Cycles were excluded if they utilized surgical sperm or preimplantation genetic testing for monogenetic/single gene defects. ICSI cycle outcomes from 2586 patients were evaluated for ploidy status of embryos.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Only patients undergoing single, euploid frozen embryo transfer were included when analyzing cycle outcomes by day of blastocyst expansion of the transferred embryo (n = 2130). Ploidy rates by the day upon which an embryo was considered to be usable (denoted, 'usable blastulation day') were determined so as to assess the contribution of aneuploidy to slow embryo development. Outcomes of euploid frozen single embryo transfers (SET) of Day 7 embryos were evaluated to assess the reproductive potential associated with embryos that were slowly developing for reasons other than aneuploidy. Analyses were adjusted by maternal age and blastocyst morphology.

MAIN RESULTS AND THE ROLE OF CHANCE:

Overall, 67.7% (n = 3508) of usable Day 5 blastocysts were euploid, 52.1% (n = 5560) of usable Day 6 blastocysts were euploid and 43.1% (n = 229) of usable Day 7 embryos were euploid (Day 5 versus Day 6: odds ratio (OR) 0.7 (95% CI, 0.64-0.76), P < 0.001; Day 5 versus Day 7: OR 0.56 (95% CI, 0.46-0.69), P < 0.001; Day 6 versus Day 7: OR 0.81 (95% CI, 0.67-0.99), P = 0.036). Stratified by Society for Assisted Reproductive Technology maternal age groups, a reduction in the prevalence of euploidy by increasing time to embryo blastulation was still seen. The sustained implantation rate (SIR) was similar after euploid SET of Days 5 and 6 embryos (overall, 68.9% (95% CI, 66.0-71.6) and 66.8% (95% CI, 63.8-69.7), respectively; P = 0.81). SIR after euploid Day 7 SET appeared slightly lower than that of Days 5 and 6 embryos (52.6% (95% CI, 35.8-69.0); (Day 5 versus Day 7: OR, 0.67 (95% CI, 0.32-1.41), P = 0.29; Day 6 versus Day 7: OR 0.58 (95% CI, 0.28-1.2), P = 0.14)) but did not achieve statistical significance.

子宮內注射HCG無法明顯提高IVF-ET胚胎著床懷孕率

Arch Gynecol Obstet. 2018 Dec;298(6):1061-1069. doi: 10.1007/s00404-018-4923-1. Epub 2018 Oct 5.

Effect of intrauterine injection of human chorionic gonadotropin before fresh embryo transfer on IVF and ICSI outcomes: a meta-analysis.

Hou W1, Shi G1, Cai B1, Ding C1, Song J1, Zhang X1, Xu Y2.

Author information

1

Reproductive Medical Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.

2

Reproductive Medical Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. xuyanwen663000@126.com.

Abstract

PURPOSE:

This analysis was performed to evaluate the effects of intrauterine injection of human chorionic gonadotropin (hCG) before fresh embryo transfer (ET) on the outcomes of in vitro fertilization and intracytoplasmic sperm injection.

METHODS:

Randomized controlled trials (RCTs) were identified by searching electronic databases. The outcomes of live birth, clinical pregnancy, implantation, biochemical pregnancy, ongoing pregnancy, ectopic pregnancy, and miscarriage between groups with and without hCG injections were analyzed. Summary measures were reported as risk ratios (RR) with 95% confidence intervals.

RESULTS:

Six RCTs on fresh embryo transfer (ET) were included in the meta-analysis. A total of 2759 women undergoing fresh ET were enrolled (hCG group n = 1429; control group n = 1330). Intrauterine injection of hCG significantly increased rates of biochemical pregnancy (RR 1.61) and ongoing pregnancy (RR 1.58) compared to controls. However, there were no significant differences in clinical pregnancy (RR 1.11), implantation (RR 1.17), miscarriage (RR 0.91), ectopic (RR 1.65) or live birth rates (RR 1.13) between the hCG group and control group.

CONCLUSION:

The current evidence for intrauterine injection of hCG before fresh ET does not support its use in an assisted reproduction cycle.

精蟲正常試管病患不需一律施行ICSI
施行傳統IVF可得到較高活產率
IVF vs ICSI (32.71% vs 24.26%).

J Hum Reprod Sci. 2019 Jul-Sep;12(3):210-215. doi: 10.4103/jhrs.JHRS_8_19.

Are we Justified Doing Routine Intracytoplasmic Sperm Injection in Nonmale Factor Infertility? A Retrospective Study Comparing Reproductive Outcomes between In vitro Fertilization and Intracytoplasmic Sperm Injection in Nonmale Factor Infertility.

INTRODUCTION:

Intracytoplasmic sperm insemination (ICSI) came into use in 1992 to improve fertilization in couples with male factor infertility undergoing in vitro fertilization (IVF) or in couples with fertilization failure in a prior IVF cycle. Our aim was to find out if routine ICSI has any additional benefit over conventional IVF in non male factor cases in modern Assisted Reproductive Technology (ART).

METHODS:

This is a retrospective single centre study undertaken at a private IVF center. A total of 350 patients with normal male factor were included in the study of which 186 underwent conventional IVF and 134 were subjected to ICSI. They were then compared for various reproductive parameters with Live Birth Rate (LBR) being the primary outcome. P value < 0.05 was considered statistically significant.

RESULTS:

Fertilization rates (89.99% vs 85.1%), Blastocyst formation rates (62.86% vs 50.61%) and clinical pregnancy rates (37.85% vs 32.35%) were found to be higher in the IVF group compared to the ICSI group though not statistically significant. The live birth rates in the IVF group was also higher than the ICSI group (32.71% vs 24.26%).

CONCLUSION:

IVF edged over ICSI in all aspects resulting in better clinical outcome with higher take home babies in non-male factor infertility. Our results show that routine ICSI should not be used as a blanket therapy for all cases in ART.

40%胚胎染色體異常發生於卵子減數分裂之前
尤其容易出現在高齡卵子

J Assist Reprod Genet. 2019 Nov 8. doi: 10.1007/s10815-019-01596-6. [Epub ahead of print]

How common is germinal mosaicism that leads to premeiotic aneuploidy in the female?

Abstract

PURPOSE:

Molecular cytogenetic analysis has confirmed that a proportion of apparently meiotic aneuploidy may be present in the germ cells prior to the onset of meiosis, but there is no clear perception of its frequency. The aim of this review is to assess the evidence for premeiotic aneuploidy from a variety of sources to arrive at an estimate of its overall contribution to oocyte aneuploidy in humans.

METHODS:

Relevant scientific literature was covered from 1985 to 2018 by searching PubMed databases with search terms: gonadal/germinal mosaicism, ovarian mosaicism, premeiotic aneuploidy, meiosis and trisomy 21. Additionally, a key reference from 1966 was included.

RESULTS:

Data from over 9000 cases of Down syndrome showed a bimodal maternal age distribution curve, indicating two overlapping distributions. One of these matched the pattern for the control population, with a peak at about 28 years and included all cases that had occurred independently of maternal age, including those due to germinal mosaicism, about 40% of the cohort. The first cytological proof of germinal mosaicism was obtained by fluorescence in situ hybridisation analysis. Comparative genomic hybridisation analysis of oocyte chromosomes suggests an incidence of up to 15% in premeiotic oocytes. Direct investigation of fetal ovarian cells led to variable results for chromosome 21 mosaicism.

CONCLUSIONS:

Oocytes with premeiotic errors will significantly contribute to the high level of preimplantation and prenatal death. Data so far available suggests that, depending upon the maternal age, up to 40% of aneuploidy that is present in oocytes at the end of meiosis I may be due to germinal mosaicism.

>40歲施行ICSI vs IVF---懷孕率並無明顯差異

J Clin Med. 2019 Oct 16;8(10). pii: E1694. doi: 10.3390/jcm8101694.

ICSI Versus Conventional IVF in Women Aged 40 Years or More and Unexplained Infertility: A Retrospective Evaluation of 685 Cycles with Propensity Score Model.

Gennarelli G1, Carosso A2, Canosa S3, Filippini C4, Cesarano S5, Scarafia C6, Brunod N7, Revelli A8, Benedetto C9.

Author information

Abstract

This study compared the cumulative live birth rates following Intracytoplasmic sperm injection (ICSI) versus conventional in vitro fertilization (cIVF) in women aged 40 years or more and unexplained infertility. A cohort of 685 women undergoing either autologous conventional IVF or ICSI was retrospectively analyzed. The effects of conventional IVF or ICSI procedure on cumulative pregnancy and live birth rates were evaluated in univariate and in multivariable analysis. In order to reduce potential differences between women undergoing either IVF or ICSI and to obtain unbiased estimation of the treatment effect, propensity score was estimated. ICSI was performed in 307 couples (ICSI group), whereas cIVF was performed in 297 couples (cIVF group), resulting in 45 and 43 live deliveries, respectively. No differences were observed in morphological embryo quality, in the number of cleavage stage embryos, in the number of transferred embryos, and in the number of vitrified embryos. As for the clinical outcome, no differences were observed in pregnancy rate, cumulative pregnancy rate, live birth rate, cumulative live birth rate, and abortion rate. The present results suggest that ICSI is not associated with increased likelihood of a live birth for unexplained, non-male factor infertility, in women aged 40 years or more.

口服腦下垂體結抗藥劑Relugolix 40mg/d x 6月治療子宮肌瘤之藥效
---可達到類似Leuprolrelin depot(1.88 mg or 3.75 mg, monthly injection)x 6月之藥效

Obstet Gynecol. 2019 Mar;133(3):423-433. doi: 10.1097/AOG.0000000000003141.

Oral Gonadotropin-Releasing Hormone Antagonist Relugolix Compared With Leuprorelin Injections for Uterine Leiomyomas: A Randomized Controlled Trial.

OBJECTIVE:

To investigate the noninferiority of relugolix compared with leuprorelin acetate in reducing heavy menstrual bleeding associated with uterine leiomyomas.

METHODS:

In a double-blind, double-dummy trial, premenopausal women with uterine leiomyomas and heavy menstrual bleeding defined as a pictorial blood loss assessment chart score of at least 120 were randomized in a 1:1 ratio to relugolix (40 mg, oral, once daily) or leuprorelin acetate (1.88 mg or 3.75 mg, monthly injection) for 24 weeks. The primary endpoint was the proportion of patients with a total pictorial blood loss assessment chart score of less than 10 for weeks 6-12. Secondary endpoints included myoma and uterine volumes, and hemoglobin levels. A sample size of 144 patients per group (n=288) was estimated to provide at least 90% power to demonstrate noninferiority (prespecified noninferiority margin -15%; one-sided 0.025 level of significance).

RESULTS:

From March 2016 to September 2017, 281 patients were randomized (relugolix, n=139, leuprorelin n=142). Demographic and baseline characteristics were well balanced; mean pictorial blood loss assessment chart score was 254.3 in the relugolix group and 263.7 in the leuprorelin group. The proportion of patients with total pictorial blood loss assessment chart score of less than 10 for weeks 6-12 was 82.2% in the relugolix group and 83.1% in the leuprorelin group, demonstrating noninferiority of relugolix compared with leuprorelin (relugolix-leuprorelin difference -0.9%; 95% CI: -10.10 to 8.35; prespecified noninferiority margin -15%; P=.001). Reductions in myoma and uterine volumes and increases in hemoglobin levels were comparable in the two groups. Relugolix was associated with an earlier effect on menstrual bleeding than leuprorelin (pictorial blood loss assessment chart score of less than 10, 64.2% vs 31.7% [relugolix-leuprorelin difference 32.5%; 95% CI: 20.95-44.13%] for weeks 2-6 and pictorial blood loss assessment chart score of 0, 52.6% vs 21.8% [30.7%; 95% CI: 19.45-42.00%] for weeks 2-6) and faster recovery of menses after treatment discontinuation (relugolix median [Q1, Q3], 37 days [32.0, 46.0]; leuprorelin median, 65 days [54.0, 77.0]). Adverse events and bone mineral density loss were similar between relugolix and leuprorelin treatment groups.

CONCLUSION:

In women with uterine leiomyomas, once-daily treatment with relugolix, an oral gonadotropin-releasing hormone antagonist, demonstrated noninferiority to monthly leuprorelin for improvement of heavy menstrual bleeding at 6-12 weeks of treatment, had a more rapid effect on menstrual bleeding, and was generally well tolerated.

卵組織冷凍植入後IVF懷孕率(3.9% to 19.3%)    活產率(3.9% to 14.0%)

Fertil Steril. 2019 Oct 6. pii: S0015-0282(19)30581-3. doi: 10.1016/j.fertnstert.2019.07.008. [Epub ahead of print]

Ovarian stimulation and assisted reproductive technology outcomes in women transplanted with cryopreserved ovarian tissue: a systematic review.

OBJECTIVE:

To systematically review reproductive outcomes of assisted reproductive technology (ART) treatment in women transplanted with frozen-thawed ovarian tissue.

DESIGN:

Systematic review in accordance with guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

SETTING:

Not applicable.

PATIENT(S):

Women undergoing ovarian tissue transplantation (OTT) and subsequent ART.

INTERVENTION(S):

Literature search in PubMed and Scopus databases.

MAIN OUTCOME MEASURE(S):

Time from OTT to initiation of ART, stimulation protocol, and conventional ART outcome measures.

RESULT(S):

Twenty studies (including 15 case reports), specifying ART treatments and outcomes of 40 women undergoing OTT were identified. Multiple stimulation protocols were applied, with the modified natural cycle as the most frequently used. In total, 195 ART cycles were performed (4.0 cycles per patient) resulting in 1.5 follicles and 1.0 mature oocyte retrieved per cycle. Empty follicle rates ranged from 23% to 35% in the three largest cohort studies. Twenty-five women (62.5%) had one or more pregnancies, of which 28.6% were lost, resulting in a total of 20 live births (22 children). Overall the pregnancy rates varied from 3.9% to 19.3% and live-birth rates from 3.9% to 14.0% per cycle in the three cohort studies. Fertility treatment was initiated shortly after OTT in some centers, while others awaited natural conception before embarking on ART treatment.

CONCLUSION(S):

The reported pregnancy and live-birth rates for women undergoing OTT and ART were considerably lower than those of the general in vitro fertilization (IVF) population, corresponding to patients with poor ovarian reserve. In general, ART outcomes are underreported, and there is a lack of consensus regarding the timing of ART in relation to OTT and the type of ovarian stimulation protocol.

男原核 與女原核大小變化可用於評估胚胎著床懷孕率
男原核與女原核大小差距於原核消失前8小時明顯小於原核消失前

Fertil Steril. 2019 Oct 23. pii: S0015-0282(19)30620-X. doi: 10.1016/j.fertnstert.2019.07.015. [Epub ahead of print]

Noninvasive embryo selection: kinetic analysis of female and male pronuclear development to predict embryo quality and potential to produce live birth.

Otsuki J1, Iwasaki T2, Enatsu N2, Katada Y2, Furuhashi K2, Shiotani M2.

Author information

1

Hanabusa Women's Clinic, Kobe, Okayama, Japan; Okayama University Assisted Reproductive Technology Center, Okayama, Japan. Electronic address: otsuki.midori.junko@gmail.com.

2

Hanabusa Women's Clinic, Kobe, Okayama, Japan.

Abstract

OBJECTIVE:

To evaluate a noninvasive method of examining euploid embryos, focusing on kinetic analyses, from second polar body extrusion to pronuclear membrane breakdown (PNMBD).

DESIGN:

Retrospective embryo cohort study.

SETTING:

Private IVF clinic.

PATIENT(S):

213 frozen-thawed single blastocyst transfers.

INTERVENTION(S):

Fertilized oocytes were recorded by means of time-lapse photography, followed by kinetic analysis of female and male pronuclei (PNs).

MAIN OUTCOME MEASURE(S):

The differences in size between the 2PNs in embryos resulting in live births compared with those of embryos from failed pregnancies were analyzed according to sequential size from early PN stages to PNMBD.

RESULT(S):

It was found that the difference in areas between male and female PNs immediately before PNMBD is a better predictor of embryo quality if this difference is below a known cutoff value. The size of male PNs 8 hours before the onset of PNMBD should be larger than female PNs (B). The difference in size between male and female PNs 8 hours before PNMBD should be larger than the difference in their size immediately before PNMBD. When normal embryos were defined using the equation (A∪C)∩B, the birth rates for in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) were 68.1% and 50.0%, respectively. For the remaining embryos, defined as abnormal according to the above criteria, birth rates were 9.4% for IVF and 4.2% for ICSI.

CONCLUSION(S):

We have developed a method for noninvasive embryo evaluation by means of the kinetic analysis of female and male PN growths. This method should enable us to select embryos that have a higher potential for healthy births.