多囊性卵巢PCO病患若體重過重，日後糖尿病機率大增 (compared to normal BW PCO)

Hum Reprod. 2016 Dec 28. doi: 10.1093/humrep/dew329. [Epub ahead of print]

Overweight and obese but not normal weight women with PCOS are at increased risk of Type 2 diabetes mellitus-a prospective, population-based cohort study.

Ollila ME1, West S1, Keinänen-Kiukaanniemi S2,3, Jokelainen J2,3, Auvinen J2,3, Puukka K4, Ruokonen A4, Järvelin MR2,5,6, Tapanainen JS1,7, Franks S8,Piltonen TT1, Morin-Papunen LC9.

Author information

Abstract

STUDY QUESTION:

What are the respective roles of polycystic ovary syndrome (PCOS), long-term weight gain and obesity for the development of prediabetes or Type 2 diabetes mellitus (T2DM) by age 46 years?

SUMMARY ANSWER:

The risk of T2DM in women with PCOS is mainly due to overweight and obesity, although these two factors have a synergistic effect on the development of T2DM.

WHAT IS KNOWN ALREADY:

PCOS is associated with an increased risk of prediabetes and T2DM. However, the respective roles of PCOS per se and BMI for the development of T2DM have remained unclear.

STUDY DESIGN, SIZE, DURATION:

In a prospective, general population-based follow-up birth cohort 1966 (n = 5889), postal questionnaires were sent at ages 14 (95% answered), 31 (80% answered) and 46 years (72% answered). Questions about oligoamenorrhoea and hirsutism were asked at age 31 years, and a question about PCOS diagnosis at 46 years. Clinical examination and blood sampling were performed at 31 years in 3127 women, and at 46 years in 3280 women. A 2-h oral glucose tolerance test (OGTT) was performed at 46 years of age in 2780 women.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Women reporting both oligoamenorrhoea and hirsutism at age 31 years and/or diagnosis of PCOS by 46 years were considered as women with PCOS (n = 279). Women without any symptoms at 31 years and without PCOS diagnosis by 46 years were considered as controls (n = 1577). The level of glucose metabolism was classified according to the results of the OGTT and previous information of glucose metabolism status from the national drug and hospital discharge registers.

MAIN RESULTS AND THE ROLE OF CHANCE:

PCOS per se significantly increased the risk of T2DM in overweight/obese (BMI ≥ 25.0 kg/m2) women with PCOS when compared to overweight/obese controls (odds ratio: 2.45, 95% CI: 1.28-4.67). Normal weight women with PCOS did not present with an increased risk of prediabetes or T2DM. The increase in weight between ages 14, 31 and 46 years was significantly greater in women with PCOS developing T2DM than in women with PCOS and normal glucose tolerance, with the most significant increase occurring in early adulthood (between 14 and 31 years: median with [25%; 75% quartiles]: 27.25 kg [20.43; 34.78] versus 13.80 kg [8.55; 20.20], P < 0.001).

LIMITATIONS, REASONS FOR CAUTION:

The diagnosis of PCOS was based on self-reporting, and the questionnaire at 46 years did not distinguish between polycystic ovaries only in ultrasonography and the syndrome. Ovarian ultrasonography was not available to aid the diagnosis of PCOS.

WIDER IMPLICATIONS OF THE FINDINGS:

These results emphasize weight management already during adolescence and early adulthood to prevent the development of T2DM in women with PCOS, as the period between 14 and 31 years seems to be a crucial time-window during which the women with PCOS who are destined to develop T2DM by 46 years of age experience a dramatic weight gain. Furthermore, our results support the view that, particularly in times of limited sources of healthcare systems, OGTT screening should be targeted to overweight/obese women with PCOS rather than to all women with PCOS.

STUDY FUNDING/COMPETING INTERESTS:

Finnish Medical Foundation; North Ostrobothnia Regional Fund; Academy of Finland (project grants 104781, 120315, 129269, 1114194, 24300796, Center of Excellence in Complex Disease Genetics and SALVE); Sigrid Juselius Foundation; Biocenter Oulu; University Hospital Oulu and University of Oulu (75617); Medical Research Center Oulu; National Institute for Health Research (UK); National Heart, Lung, and Blood Institute (grant 5R01HL087679-02) through the STAMPEED program (1RL1MH083268-01); National Institute of Health/National Institute of Mental Health (5R01MH63706:02); ENGAGE project and grant agreement HEALTH-F4-2007-201413; EU FP7 EurHEALTHAgeing-277849 European Commission and Medical Research Council, UK (G0500539, G0600705, G1002319, PrevMetSyn/SALVE) and Medical Research Center, Centenary Early Career Award. The authors have no conflicts of interests.

高齡婦女不需全盤使用ICSI授精
精蟲品質正常仍可使用IVF

Hum Reprod. 2017 Jan;32(1):119-124. Epub 2016 Nov 16.

The role of intracytoplasmic sperm injection in non-male factor infertility in advanced maternal age.

Tannus S1, Son WY2, Gilman A2, Younes G2, Shavit T2, Dahan MH2.

Author information

Abstract

STUDY QUESTION:

Does ICSI improve reproductive outcomes compared with conventional IVF when used for non-male factor infertility in women aged 40 years and over?

SUMMARY ANSWER:

There is no advantage of ICSI over conventional IVF in women aged 40 years and over when used for non-male factor infertility.

WHAT IS KNOWN ALREADY:

The use of ICSI has increased dramatically in recent years and is being applied for indications other than male factor infertility. Currently, ICSI is used in 65% of IVF cycles in Europe and in 76% of cycles in the USA. Despite its increase use, there is no clear evidence of a benefit in using ICSI over conventional IVF. Older women undergoing infertility treatments are at an increased risk of having diminished ovarian reserve and lower oocyte quality, which could make ICSI the preferred insemination method in this group. However, studies that have examined the benefits of ICSI in this age group are lacking.

STUDY DESIGN, SIZE, DURATION:

A retrospective, single center study included women, aged 40-43 years, who underwent IVF treatments for non-male factor infertility between January 2012 until June 2015.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

A total of 745 women were included in the study. Of these, 490 women underwent ICSI and 255 women underwent conventional IVF. In order to be included in the study, women had to be at least 40 years of age at the beginning of ovarian stimulation and their male partner had to have normal sperm parameters according to World Health Organisation (WHO) fifth edition. Exclusion criteria included: more than three previous IVF cycles, a history of fertilization failure or low fertilization (<50%), the use of donor or frozen oocytes and the use of donor or frozen sperm samples. The primary outcome was the live birth rate. Secondary outcomes included fertilization rates, fertilization failure and embryo quality.

MAIN RESULTS AND THE ROLE OF CHANCE:

Baseline characteristics were similar between the two groups, except for the number of previous IVF cycles, which was higher in the ICSI group (1.0 vs. 0.6, P = 0.0001). Despite similar numbers of oocytes retrieved (7.2 vs. 6.5), when examining oocytes maturity (performed 2 h after oocyte retrieval in the ICSI group and after 18 h in the conventional IVF group), the conventional IVF group had a higher number of Metaphase II (MII) oocytes (6.1 vs. 4.7, P < 0.0001). The conventional IVF group also had higher numbers of zygotes formed (4.48 vs. 3.66, P = 0.001), more cycles with embryos transferred at the blastocyst stage (36 vs. 26%, P = 0.005) and more cycles where embryos were available for cryopreservation (26.4 vs. 19.7%, P = 0.048), compared with the ICSI group. The fertilization rates (64 vs. 67%) and fertilization failure (9.0 vs. 9.7%) were similar. After logistic regression analysis controlling for confounders, the live birth rates were similar between the groups (11.9 vs. 9.6%). Subgroup analyses of women undergoing their first IVF cycle and women with ≤3 oocytes retrieved did not show an advantage of ICSI over conventional IVF.

誘導排卵前使用雌激素或含雌激素之避孕藥對於IVF有不良影響

Hum Reprod. 2016 Dec 19. doi: 10.1093/humrep/dew325. [Epub ahead of print]

Effect of pretreatment with oral contraceptives and progestins on IVF outcomes in women with polycystic ovary syndrome.

Wei D1,2, Shi Y1,2, Li J1,2, Wang Z1,2, Zhang L1,2, Sun Y3, Zhou H4, Xu Y5, Wu C6, Liu L7, Wu Q8, Zhuang L9, Du Y3, Li W3, Zhang H10, Legro RS11, Chen ZJ12,2,3.

Author information

Abstract

STUDY QUESTION:

Do oral contraceptives (OCs) and progestins impact live birth rate of IVF when used for cycle scheduling in women with polycystic ovary syndrome (PCOS)?

SUMMARY ANSWER:

OCs used for scheduling IVF cycle were associated with lowered rates of pregnancy and live birth after fresh embryo transfer, whereas progestins used for this purpose yield higher rates of pregnancy and live birth than OCs.

WHAT IS KNOWN ALREADY:

Due to oligo-menorrhea in PCOS, OCs and progestin are extensively used to schedule the start of an IVF cycle in women with PCOS. Little is known about the effect of such pretreatments on outcomes, especially, the rate of live birth.

STUDY DESIGN, SIZE, DURATION:

This was a nested cohort study and secondary analysis of a multicenter randomized trial, which was designed to compare live birth rate after fresh embryo transfer vs frozen embryo transfer (FET) in women with PCOS (Frefro-PCOS). A total of 1508 women were enrolled from 14 centers between June 2013 and May 2014.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

At the discretion of local investigators, subjects were instructed to wait for spontaneous menses (Control group, n = 323), or were prescribed progestins (P group, n = 283) or OCs (OCs group, n = 902) to induce menstruation prior to the start of ovarian stimulation. GnRH antagonist protocol was initiated at Day 2 or 3 of induced or spontaneous menses cycle. The rates of pregnancy, pregnancy loss and live birth after either fresh embryo transfer or FET were compared among these three groups.

MAIN RESULTS AND THE ROLE OF CHANCE:

With fresh embryo transfer, women with OC-induced menses had lower rates of clinical pregnancy (48.8% vs 63.6%, relative rate (RR): 0.77, 95% CI: 0.66-0.89) and live birth (36.1% vs 48.1%, RR: 0.75, 95% CI: 0.61-0.92) than women with spontaneous menses. With freeze-all and deferred FET, women with OC-induced menses had a similar pregnancy rate but a higher pregnancy loss rate (27.7% vs 13.0%, RR: 2.13, 95% CI: 1.28-3.52) after FET than women with spontaneous menses. The live birth rate after FET in women with OC-induced menses, progestin-induced menses and spontaneous menses was 49.4%, 50.7% and 60.2%, respectively (P = 0.06). Progestin-induced menses was associated with similar rates of pregnancy, pregnancy loss and live birth after transfer of either fresh or frozen embryos compared with spontaneous menses. Multivariate logistic regression analysis showed that OCs used for menses induction was associated with lower rate of live birth.

使用provera (10mg/d, since M3)於誘導排卵
優點: 可取代GnRH agonist, 有效防止99%之LH surge
缺點: 增加誘導排卵針劑量約500iu

Medicine (Baltimore). 2016 Mar;95(9):e2939. doi: 10.1097/MD.0000000000002939.

Controlled Ovarian Stimulation Using Medroxyprogesterone Acetate and hMG in Patients With Polycystic Ovary Syndrome Treated for IVF: A Double-Blind Randomized Crossover Clinical Trial.

Wang Y1, Chen Q, Wang N, Chen H, Lyu Q, Kuang Y.

Author information

Abstract

Ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation is a current challenge for patients with polycystic ovarian syndrome (PCOS). Our previous studies indicated that progestin can prevent premature luteinizing hormone (LH) surge or moderate/severe OHSS in the general subfertile population, both in the follicular-phase and luteal-phase ovarian stimulation but it is unclear if this is true for patients with PCOS. The aim of the article was to analyze cycle characteristics and endocrinological profiles using human menopausal gonadotropin (hMG) in combination with medroxyprogesterone acetate (MPA) for PCOS patients who are undergoing IVF/intracytoplasmic sperm injection (ICSI) treatments and investigate the subsequently pregnancy outcomes of frozen embryo transfer (FET). In the randomized prospective controlled study, 120 PCOS patients undergoing IVF/ICSI were recruited and randomly classified into 2 groups according to the ovarian stimulation protocols: hMG and MPA (group A, n = 60) or short protocol (group B, n = 60). In the study group, hMG (150-225IU) and MPA (10 mg/d) were administered simultaneously beginning on cycle day 3. Ovulation was cotriggered by a gonadotropinreleasing hormone (GnRH) agonist (0.1 mg) and hCG (1000IU) when dominant follicles matured. A short protocol was used as a control. The primary end-point was the ongoing pregnancy rate per transfer and incidence of OHSS. Doses of hMG administrated in group A are significantly higher than those in the controls. LH suppression persisted during ovarian stimulation and no incidence of premature LH surge was seen in both groups. The fertilization rate and the ongoing pregnant rate in the study group were higher than that in the control. The number of oocytes retrieved, mature oocytes, clinical pregnancy rates per transfer, implantation rates, and cumulative pregnancy rates per patient were comparable between the 2 groups. The incidence of OHSS was low between the 2 groups, with no significant difference. The study showed that MPA has the advantages of an oral administration route, easy access, more control over LH levels. A possible reduction in the incidence of moderate or severe OHSS with the MPA protocol should be viewed with caution as the data is small. Large randomized trials with adequate sample size remain necessary.

Letrozole 使用於IVF誘導排卵
並不會明顯提高畸形率
可能可下降流產率

Hum Reprod. 2016 Nov 7. [Epub ahead of print]

No increased risk of major congenital anomalies or adverse pregnancy or neonatal outcomes following letrozole use in assisted reproductive technology.

Tatsumi T1,2, Jwa SC3,4, Kuwahara A5, Irahara M5, Kubota T2, Saito H1.

Author information

Abstract

STUDY QUESTION:

Does letrozole use increase the risk of major congenital anomalies and adverse pregnancy and neonatal outcomes in fresh, single-embryo transfer?

SUMMARY ANSWER:

Letrozole significantly decreases the risk of miscarriage and does not increase the risk of major congenital anomalies or adverse pregnancy or neonatal outcomes compared with natural cycles in patients undergoing ART.

WHAT IS KNOWN ALREADY:

Letrozole is the most commonly used aromatase inhibitor for mild ovarian stimulation in ART. However, its safety in terms of pregnancy and neonatal outcomes is unclear.

STUDY DESIGN SIZE, DURATION:

This retrospective cohort study used data from the Japanese national ART registry from 2011 to 2013.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

A total of 3136 natural cycles and 792 letrozole-induced cycles associated with fresh, single-embryo transfer and resulting in a clinical pregnancy were included in the analysis. The main pregnancy outcomes were miscarriage, ectopic pregnancy and still birth, and the neonatal outcomes were preterm delivery, low birth weight, small/large for gestational age and major congenital anomalies. Terminated pregnancies were included in the analysis of major congenital anomalies. Odds ratios (ORs) and 95% CIs were calculated using multivariate logistic regression analysis adjusted for maternal age and calendar year.

MAIN RESULTS AND THE ROLE OF CHANCE:

The risk of miscarriage was significantly lower in women administered letrozole (adjusted OR [aOR], 0.37, 95% CI, 0.30-0.47, P < 0.001). There was no significant difference in the overall risk of major congenital anomalies between the two groups (natural cycle 1.5% vs letrozole 1.9%, aOR, 1.24, 95% CI, 0.64-2.40, P = 0.52), and no increased risk for any specific organ system. Subgroup analysis demonstrated that the risk of major congenital anomalies was not increased in patients who underwent either in vitro fertilization or ICSI, or in those who received early cleavage stage or blastocyst embryo transfer. All other pregnancy and neonatal outcomes were comparable between the two groups.

誘導排卵針施打過程&懷孕早期可能會造成甲狀腺刺激素TSH上升

Reprod Fertil Dev. 2015 Oct 8. doi: 10.1071/RD15172. [Epub ahead of print]

Thyroid function and autoimmunity during ovarian stimulation for intracytoplasmic sperm injection.

Mintziori G, Goulis DG, Kolibianakis EM, Slavakis A, Bosdou J, Grimbizis G, Tarlatzis BC.

Abstract

The aim of the present study was to assess changes in thyroid function and thyroid autoimmunity (TAI) throughout ovarian stimulation (OS) for intracytoplasmic sperm injection (ICSI) and the association of these changes with ICSI outcome. A flexible gonadotrophin-releasing hormone (GnRH) antagonist protocol was used in 42 women and their thyroid function and TAI were assessed at baseline and five times during OS (Days 3 and 5 of the menstrual cycle, the day of hCG administration, the day of ovum pick-up and the day of the pregnancy test). The primary outcome measure was the change in thyroid function throughout OS. No overall change was recorded in thyrotropin-stimulating hormone (TSH) concentrations throughout OS (P = 0.066). In women who became pregnant (n = 8), an increase in TSH concentrations was noted on the day of the pregnancy test compared with Day 3 of the menstrual cycle (3.410 ± 1.200 vs 2.014 ± 0.950 μIU mL-1, respectively; P = 0.001; mean ± s.d.). TAI was present in 11 of 42 women. Biochemical pregnancy was negatively correlated with changes in TSH (r = -0.7, P = 0.004). No such association was noted regarding the live birth rate. The present study provides evidence that TSH concentrations could increase during OS, especially in women who become pregnant.

添加VEGF血管內皮生長因子(200ng/ml)於原始卵子培養液中達20小時，可提高未成熟卵子IVM成熟率及囊胚率

Reprod Fertil Dev. 2016 Dec 12. doi: 10.1071/RD16321. [Epub ahead of print]

Presence of vascular endothelial growth factor during the first half of IVM improves the meiotic and developmental competence of porcine oocytes from small follicles.

Bui TM, Nguyễn KX, Karata A, Ferré P, Trần MT, Wakai T, Funahashi H.

Abstract

The aim of the present study was to investigate the effect of vascular endothelial growth factor (VEGF) on the meiotic and developmental competence of porcine oocytes from small follicles (SF; 0.5-3mm diameter). When cumulus-oocyte complexes (COCs) from medium-sized follicles (MF; 3-6mm diameter) and SF were cultured for IVM, the maturation rates were significantly higher for oocytes from MF than SF. Concentrations of VEGF in the medium were significantly higher for COCs cultured from MF than SF. When COCs from SF were exposed to 200ngmL-1 VEGF during the first 20h of IVM, the maturation rate improved significantly and was similar to that of oocytes derived from MF. The fertilisability of oocytes was also significantly higher than that of VEGF-free SF controls. Following parthenogenetic activation, the blastocyst formation rate improved significantly when SF COC culture was supplemented with 200ngmL-1 VEGF, with the rate similar to that of oocytes from MF. The results of the present study indicate that VEGF markedly improves the meiotic and developmental competence of oocytes derived from SF, especially at a concentration of 200ngmL-1 during the first 20h of IVM.

血癌病患之精蟲染色體異常率偏高
化療後染色體異常率更高
化療後2年以上才逐漸回復正常

Fertil Steril. 2016 Oct 31. pii: S0015-0282(16)62914-X. doi: 10.1016/j.fertnstert.2016.10.001. [Epub ahead of print]

Impact of Hodgkin or non-Hodgkin lymphoma and their treatments on sperm aneuploidy: a prospective study by the French CECOS network.

Martinez G1, Walschaerts M2, Le Mitouard M1, Borye R1, Thomas C1, Auger J3, Berthaut I4, Brugnon F5, Daudin M6, Moinard N6, Ravel C7, Saias J8,Szerman E9, Rives N10, Hennebicq S11, Bujan L12.

Author information

Abstract

OBJECTIVE:

To assess sperm production and aneuploidy in Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) before and after treatments.

DESIGN:

Multicenter, prospective, longitudinal study of lymphoma patients analyzed before treatment and after 3, 6, 12, and 24 months.

SETTING:

University hospitals.

PATIENT(S):

Forty-five HL and 13 NHL patients were investigated before and after treatment. Treatment regimens were classified in two groups: ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) with or without (±) radiotherapy, and CHOP (doxorubicin, cyclophosphamide, vincristine, prednisone)/MOPP-ABV (mechlorethamine, oncovin, procarbazine, prednisone-doxorubicin, bleomycin, vinblastine). A control group of 29 healthy men was also studied.

INTERVENTION(S):

Semen analyses and aneuploidy study by FISH were performed at each time point.

MAIN OUTCOME MEASURE(S):

Comparison of mean sperm characteristics and percentage of sperm aneuploidy rates before and after treatment.

RESULT(S):

Before treatment, HL and NHL men had altered semen characteristics and higher sperm aneuploidy rates (median 0.76 [interquartile range 0.56-0.64]) than the control group (0.54 [0.46-0.74]). After treatment, sperm production was significantly lowered 3 and 6 months after ABVD ± radiotherapy or CHOP/MOPP-ABV. After ABVD ± radiotherapy, the aneuploidy rate increased significantly only at 3 months, and values obtained 1 or 2 years later were lower than pretreatment values. In contrast, in the CHOP/MOPP-ABV treatment group, semen characteristics and aneuploidy rate did not return to normal levels until 2 years after treatment.

CONCLUSION(S):

Lymphoma itself has consequences on sperm aneuploidy frequency before treatment. Moreover, lymphoma treatments have deleterious effects on sperm chromosomes related to treatment type and time since treatment. Patient counseling is essential concerning the transient but significant sperm aneuploidy induced by lymphoma and its treatments.

PGD診斷胚胎染色體鑲嵌體時不建議植入
尤其第2, 7, 13, 14, 15, 16, 18, and 21染色體三套之鑲嵌體風險更高
其他染色體之鑲嵌體風險較低但不保證胚胎日後染色體會回復正常

Fertil Steril. 2016 Nov 11. pii: S0015-0282(16)62921-7. doi: 10.1016/j.fertnstert.2016.10.006. [Epub ahead of print]

Diagnosis and clinical management of embryonic mosaicism.

Sachdev NM1, Maxwell SM2, Besser AG1, Grifo JA1.

Author information

Abstract

Embryonic mosaicism occurs when two or more cell populations with different genotypes are present within the same embryo. New diagnostic techniques for preimplantation genetic screening (PGS), such as next-generation sequencing, have led to increased reporting of mosaicism. The interpretation of mosaicism is complicated because the transfer of some mosaic embryos has resulted in live births. Mosaic embryos may represent a third category between normal (euploidy) and abnormal (aneuploidy). This category of mosaic embryos may be characterized by decreased implantation and pregnancy potential as well as increased risk of genetic abnormalities and adverse pregnancy outcomes. Euploid embryos should be preferentially transferred over mosaic embryos. Genetic counseling is necessary before the transfer of a mosaic embryo is considered. Certain types of mosaic embryos should be preferentially transferred over others. Transfer of embryos with mosaic trisomies 2, 7, 13, 14, 15, 16, 18, and 21 may pose the most risk of having a child affected with a trisomy syndrome; however, the transfer of embryos with mosaic monosomies or other mosaic trisomies are not devoid of risk. Patients must be counseled about the risk of undetected monosomies or trisomies within a biopsy specimen as well as the risk of intrauterine fetal demise or uniparental disomy with the transfer of mosaic embryos. Until more data are available, patients should be encouraged to undergo another cycle to obtain euploid embryos, when possible, rather than transferring a mosaic embryo.

一般而言多囊性卵巢病患之AMH多>4ng/ml以上，
多囊性卵巢病患若AMH偏低(<3)，日後心血管,糖尿病等代謝性疾病機率較高

Fertil Steril. 2016 Nov 11. pii: S0015-0282(16)62927-8. doi: 10.1016/j.fertnstert.2016.10.009. [Epub ahead of print]

Antimüllerian hormone levels and cardiometabolic risk in young women with polycystic ovary syndrome.

Feldman RA1, O'Neill K1, Butts SF1, Dokras A2.

Author information

Abstract

OBJECTIVE:

To determine the association between antimüllerian hormone (AMH) levels and metabolic syndrome (MetSyn) in young women with polycystic ovary syndrome (PCOS).

DESIGN:

Cross-sectional study.

SETTING:

Academic PCOS center.

PATIENT(S):

A total of 252 women aged 18-46 years with PCOS.

INTERVENTION:

None.

MAIN OUTCOME MEASURE(S):

Association of AMH with markers of cardiometabolic risk and MetSyn.

RESULT(S):

The median AMH level was 5.1 ng/mL (interquartile range [IQR] 3.0-8.1), and prevalence of MetSyn was 23.8%. AMH levels positively correlated with total T, high-density lipoprotein (HDL) cholesterol, and SHBG and negatively correlated with fasting glucose, homeostasis-model assessment of insulin resistance, body mass index (BMI), and systolic and diastolic blood pressure. A single-unit decrease in AMH was associated with an 11% increase in odds of MetSyn (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.03-1.20); the strength of this association was maintained in the multivariate model (OR 1.09, 95% CI 1.01-1.18) adjusting for age and race. Subjects with AMH values in the lowest tertile were twice as likely as those in the highest tertile to have MetSyn (adjusted OR 2.1, 95% CI 1.01-4.3). Total T was not associated with MetSyn or its individual components.

CONCLUSION(S):

Our findings indicate that in young women with PCOS, low AMH levels predict a greater risk of MetSyn. The role of AMH, an established biomarker of ovarian reserve, in risk stratification of cardiometabolic risk in obese women with PCOS needs to be clarified in longitudinal studies and in the perimenopausal population.

胚胎培養過程添加微量胰島素(10ug/ml)或許可以提高胚胎細胞分裂數目，分裂品質&囊胚率

Fertil Steril. 2016 Dec 1. pii: S0015-0282(16)62965-5. doi: 10.1016/j.fertnstert.2016.11.003. [Epub ahead of print]

Integrating insulin into single-step culture medium regulates human embryo development in vitro.

Fawzy M1, Sabry M2, Nour M2, Abdelrahman MY2, Roshdy E3, Magdi Y4, Abdelghafar H2.

Author information

Abstract

OBJECTIVE:

To evaluate the effect of supplementing single-step embryo culture medium with insulin on human embryo development.

DESIGN:

Comparative study.

SETTING:

Two private centers.

PATIENT(S):

The study involved a sibling oocyte split of 5,142 retrieved oocytes from 360 patients.

INTERVENTION(S):

Sibling oocytes split after intracytoplasmic sperm injection for culture from day 0 through day 5 or 6 in insulin-supplemented or control medium. Women were split to receive their embryos from insulin-supplemented or control medium.

MAIN OUTCOME MEASURE(S):

Clinical pregnancy rate.

RESULT(S):

There were significantly higher rates of clinical, ongoing, and twin pregnancies in the insulin-supplemented arm than in the control arm. On day 3, embryo quality and compaction were higher in insulin-supplemented medium. On day 5, insulin supplementation showed higher rates of blastocyst formation, quality, and cryopreservation.

CONCLUSION(S):

Insulin supplementation of single-step embryo culture medium from day 0 through day 5 or 6 improved clinical pregnancy rate and human embryo development. However, these findings need further confirmation through a multicenter randomized controlled trial that may include other patient populations and different culture media.

Day5-6囊胚期胚胎約有60個細胞
Day0~Day5期間胚胎平均18小時分裂一次

高達73%IVF胚胎含有異常染色體之胚葉細胞
高達20%卵子含有異常染色體
高達9%精蟲含有異常染色體

http://link.springer.com/article/10.1007%2Fs10815-016-0845-7

大規模統計發現胚胎高達73%呈現染色體異常
59%呈現染色體正常染色體與異常染色體合併(鑲嵌體異常)
此比例說明胚胎植入後高流產率

Hum Reprod Update. 2011 Sep-Oct;17(5):620-7. doi: 10.1093/humupd/dmr014. Epub 2011 Apr 29.

Chromosomal mosaicism in human preimplantation embryos: a systematic review.

van Echten-Arends J1, Mastenbroek S, Sikkema-Raddatz B, Korevaar JC, Heineman MJ, van der Veen F, Repping S.

Author information

Abstract

BACKGROUND:

Although chromosomal mosaicism in human preimplantation embryos has been described for almost two decades, its exact prevalence is still unknown. The prevalence of mosaicism is important in the context of preimplantation genetic screening in which the chromosomal status of an embryo is determined by the analysis of a single cell from that embryo.

METHODS:

Here we report a systematic review and meta-analysis of studies on the chromosomal constitution of human preimplantation embryos. In 36 studies, out of 2117 citations that met our search criteria, data were provided extensively enough to allow classification of each analysed embryo with prespecified criteria for its chromosomal makeup. The main outcome of this classification was the prevalence of chromosomal mosaicism in human preimplantation embryos.

RESULTS:

A total of 815 embryos could be classified. Of these, 177 (22%) were diploid, 599 (73%) were mosaic, of which 480 (59% of the total number of embryos) were diploid-aneuploid mosaic and 119 (14% of the total number of embryos) were aneuploid mosaic, and 39 (5%) contained other numerical chromosomal abnormalities. The distribution of the embryos over these categories was associated with the developmental stage of the embryos, the method used for analysis and the number of chromosomes analysed.

CONCLUSIONS:

Diploid-aneuploid mosaicism is by far the most common chromosomal constitution in spare human preimplantation embryos after IVF. This undermines the reliable determination of the ploidy status of a cleavage-stage embryo based on the analysis of a single cell. Future research should determine the origin and developmental potential of mosaic embryos.

使用胚胎即時監測無法有效監測胚胎染色體是否正常(僅16%-47%準確性)

Fertil Steril. 2016 Dec 6. pii: S0015-0282(16)63003-0. doi: 10.1016/j.fertnstert.2016.11.005. [Epub ahead of print]

Time-lapse morphokinetic assessment has low to moderate ability to predict euploidy when patient- and ovarian stimulation-related factors are taken into account with the use of clustered data analysis.

Mumusoglu S1, Yarali I2, Bozdag G1, Ozdemir P3, Polat M2, Sokmensuer LK4, Yarali H5.

Author information

Abstract

OBJECTIVE:

To study whether time-lapse morphokinetic (TLM) assessment predicts ploidy status when patient- and ovarian stimulation-related factors are taken into account.

DESIGN:

Retrospective cohort study.

SETTING:

Private IVF clinic.

PATIENT(S):

In total, 103 consecutive patients (415 blastocysts) were included. All embryos were individually cultured in a time-lapse incubator from intracytoplasmic sperm injection up to trophectoderm biopsy. Following trophectoderm biopsy on day 5 or 6, blastocysts were vitrified and 23 TLM parameters were analyzed.

INTERVENTION(S):

Correlations between patient- and ovarian stimulation-related factors and TLM parameters were tested in a multilevel mixed-effects linear regression model and assessed by means of intraclass correlation coefficient (ICC).

MAIN OUTCOME MEASURE(S):

Predictive ability of TLM parameters for euploidy.

RESULT(S):

The majority of TLM parameters had ICCs of 16%-47%. None of the patient- or ovarian stimulation-related factor had any systematic effect on any TLM parameter; however, body mass, total FSH dose, duration of infertility, number of previous cycles, antral follicle count, ovarian stimulation protocol, and E2 on the trigger day had a significant impact on some TLM parameters. With the use of multilevel mixed-effects logistic regression analysis, of the ten TLM parameters that were initially noted to be significantly different among euploid and aneuploid blastocysts in the univariate analysis, only five remained significant. However, the areas under the receiver operating characteristic curves at regression analysis were low, ranging from 0.55 to 0.63.

CONCLUSION(S):

Five TLM parameters, all related to timing of blastocyst development, have limited ability to predict euploidy when patient- and ovarian stimulation-related factors are taken into account.