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Objective To investigate the predictive value of endometrial thickness (EMT) for live birth when a lower threshold of EMT is not employed for embryo transfer (ET). Design Retrospective study Setting Academic assisted reproduction center Patient(s) All women who underwent fresh or frozen-thawed ET at the Koc University Hospital Assisted Reproduction Unit between October 2016 and August 2019 Intervention(s) After ruling out endometrial pathology, blastocyst transfer was planned regardless of the EMT in the absence of increased serum progesterone level on the trigger day in fresh embryo transfer cycles or before commencing progesterone treatment in artificially prepared frozen-thawed ET cycles. Main Outcome Measure(s) The primary outcome was live birth. Live birth and miscarriage rates per ET were stratified according to fresh and frozen-thawed ET cycles for each millimeter of endometrial thickness. Receiver operator characteristic curve analyses were performed to evaluate the predictive value of EMT for live birth. Result(s) A total of 560 ET cycles, 273 fresh and 287 frozen-thawed, were included in the study. Relevant patient characteristics as well as EMTs were similar between women who achieved a live birth and those who did not after fresh or frozen-thawed ET. There was no linear association between EMT and live birth or miscarriage rates. Area under the curve values for EMT to predict live birth after fresh, frozen-thawed, and all ETs were 0.56, 0.47, and 0.52, respectively. Conclusion(s) Our results showed that the EMT was not predictive for live birth in either fresh or frozen-thawed ET cycles. Once intracavitary pathology and inadvertent progesterone exposure were excluded, women with thinner EMTs should not be denied their potential for live birth because it is comparable to that of those with thicker EMT.

Research question Does subcutaneous progesterone provide similar live birth or ongoing pregnancy rates as vaginal progesterone in frozen embryo transfer (FET) cycles? Design Retrospective cohort study (n = 214 women), consisting of 107 women who received subcutaneous progesterone for FET in artificial cycles and 107 women receiving vaginal progesterone who were matched for age and treatment cycle rank acted as controls. All embryos were transferred in an artificial cycle with 6 mg per day oral oestradiol valerate starting on the second or third day of the menstrual cycle. Patients underwent transvaginal ultrasound on the 10th day of priming, and subcutaneous progesterone (50 mg/day) or vaginal progesterone (180 mg/day) was started if the endometrium had a trilinear pattern regardless of its thickness. Embryo transfer was carried out on the sixth day of progesterone administration. Oestradiol and progesterone were continued until a negative pregnancy test, 10 days after the transfer, or until the completion of 10th gestational week. Main outcome measures were live birth or ongoing pregnancy rates. Results Baseline characteristics were similar between the groups. Positive pregnancy test rates (64.5% versus 58.9%; P = 0.40; RR 1.1; 95% CI 0.89 to 1.35), live birth or ongoing pregnancy rates (39.3% versus 35.5%; P = 0.57; RR 1.11; 95% CI 0.78 to 1.56) and miscarriage rates (29% versus 25.5%; P = 0.68; RR 1.08; 95% CI 0.76 to 1.55) were similar in the subcutaneous progesterone and vaginal progesterone groups, respectively. Conclusions Subcutaneous progesterone seems to be an effective alternative to vaginal progesterone in patients undergoing FET. Randomized controlled trials comparing it with different progesterone preparations, routes and protocols are needed to better define its role.

Study question Do livebirth rate (LBR), obstetric and perinatal outcomes vary between frozen embryo transfers (FET) in the first or subsequent menstrual cycles following a freeze-all approach? Summary answer Immediate FET has a higher LBR and similar perinatal outcomes than delayed FET. Quantitative synthesis of available literature shows an increased LBR with immediate transfer. What is known already Whether FET should be done in the first menstrual cycle following oocyte collection (OC) is controversial and the duration of a possible detrimental effect of supraphysiological sex steroid levels on pregnancy outcome is unknown. A multinational survey centers showed that, 61% of clinicians prefer to wait for a washout period before proceeding to FET, even after a failed fresh embryo transfer. Limited number of studies compared FET in the first menstrual cycle with delayed FET in a subsequent cycle with varying results. There is limited data on obstetric outcomes of pregnancies resulting from FET in the first menstrual cycle. Study design, size, duration 198 women who underwent a freeze-all cycle followed by FET between July 2017 and June 2020 were included. 119 FET in the first menstrual cycle (30 days from oocyte collection) were retrospectively compared. MEDLINE was searched on 01 January 2021 using relevant keywords. Cohort studies comparing immediate versus delayed transfer following freeze all cycles were included and quantitative summary for LBR was obtained. Participants/materials, setting, methods Freeze-all was undertaken when (i) the woman is deemed to be at high risk for OHSS, (ii)serum progesterone level is > 1.5 ng/ml on the day of trigger, (iii)preimplantation genetic testing is planned, (iv)the woman will undergo surgery prior to ET, (v)couple preference. Main results and the role of chance Baseline characteristics were similar between the groups except for antral follicle count (22 vs 18, MD = 5, 95% CI = 0 to 8), and number of metaphase-two oocytes (13 vs 10, MD = 3, 95% CI = 1 to 6) all of which were significantly higher in the immediate transfer group. Clinical pregnancy rate (CPR) per ET was similar in two groups (50.4% vs 44.3%, RR = 1.14, 95% CI = 0.84 to 1.54). Miscarriage rate per pregnancy was significantly lower (12.3 vs 31.1, RR = 0.40, 95% CI = 0.19 to 0.84) and LBR per ET was significantly higher (42.9 vs 26.6, RR = 1.61, 95% CI = 1.06 to 2.46) in the immediate transfer group. Median gestational age at delivery was similar (267.5 (262.5–273) vs 268 (260–271.5) days, MD = 1.00, 95% CI= –4.00 to 5.00). Median birthweight was significantly higher in the delayed transfer group (3520 vs 3195 grams, MD= –300, 95% CI= –660 to –20 grams). Birthweight percentile, height at birth and head circumference were similar between groups. Literature search revealed 1712 studies from which nine were eligible for quantitative summary. Cumulative risk ratio showed a 10% increase in LBR with immediate transfer compared to delayed transfer (RR = 1.10, 95% CI = 1.01 – 1.20, I2=67%, 17369 embryo transfers). Limitations, reasons for caution Our study is limited by its retrospective design and relatively limited sample size for multivariate analyses. Yet, it is reassuring that the majority of our findings are consistent with previous publications. Wider implications of the findings: The hypotheses generated by our retrospective findings, i.e., FET in the immediate menstrual cycle resembling fresh ETs with strong trends towards lower birthweight and lower incidence of preeclampsia is noteworthy for the design of future studies, and these outcomes should be followed and reported. Trial registration number None

Study question Does the presence of endometrioma during ovarian stimulation affect blastulation and clinical pregnancy rates (CPR)? Summary answer Blastulation rates were similar in women with endometrioma compared to women without. Likewise, CPR were comparable. What is known already Although relationship of endometriosis and subfertility is well-established, its mechanism is still under investigation. Decreased oocyte quality, resulting from anatomical and/or inflammatory factors is one of the prominent culprits. Most studies regarding endometriosis and oocyte quality are highly heterogeneous and effect of endometriosis on oocyte quality is yet to be determined. Blastulation is thought as a surrogate marker for oocyte quality. Thus, it may be possible that detrimental effect of the presence of endometrioma during ovarian stimulation can be indirectly assessed by blastulation. Study design, size, duration Records of all women who underwent assisted reproductive technology treatment at Koc University Hospital Assisted Reproduction Unit between 2016 and October 2020 were screened for this retrospective study. All women who had endometrioma(s) during ovarian stimulation were included in the study group (EG) (n = 71). They were matched with women diagnosed with tubal factor or unexplained infertility who underwent oocyte pickup within the same period to form the control group (CG) (n = 104). Participants/materials, setting, methods All women underwent antagonist or long protocol. All embryos were cultured until blastocyst stage regardless of the number of oocytes or embryos available. Size/location of endometriomas, number of oocytes retrieved, number of available blastocysts, positive pregnancy test per cycle and clinical pregnancy rate per cycle were recorded. Blastulation rate was calculated as number of available blasts divided by the number of metaphase-II oocytes. Embryos were transferred in a fresh or artificially prepared frozen-thawed cycle. Main results and the role of chance There were 71 women in EG and 104 women in CG, which included 30 women with tubal and 74 with unexplained infertility. Median endometrioma size was 26 mm(22–33). Twenty-three patients in EG had history of endometrioma excision (31.3%). Median age [35.0 years (31.0–39.0) vs 34 (32.0–36.0), p = 0.26] and serum AMH levels [1.8 (1.1 - 4.2) vs 2.3 (1.3 - 3.7) ng/dL, p = 0.91] were similar in EG and CG, respectively. Body mass index in kg/m2 [21.8 (20.2–24.6) vs 24 (21.5–27.9), p Positive pregnancy test per cycle was similar at 53.5% vs 61.5% in EG and CG, respectively (p = 0.3). CPR were similar between the EG and CG (45% vs 58%, respectively, p = 0.10). Limitations, reasons for caution Retrospective design, lack of live birth information are the main limitations of our study. Wider implications of the findings: Presence of endometrioma during ovarian stimulation does not seem to adversely affect blastulation rates. While this is reassuring regarding oocyte quality, further research is required to assess its effect on live birth. Trial registration number Not applicable

The aim of this retrospective cohort study was to compare the effectiveness of the new flexible progestin primed ovarian stimulation (fPPOS) protocol with the flexible gonadotropin-releasing-hormone antagonist (GnRH-ant) protocol in women with decreased ovarian reserve (DOR). Twenty-seven women who underwent fPPOS and 54 age-matched women who received GnRH-ant for pituitary suppression were included in the study. All women had DOR and underwent oocyte cryopreservation. Three-hundred IU/day FSH was started on cycle day 2-3 and 0.25 mg/day GnRH-ant or 10 mg/day medroxyprogesterone acetate was started when the leading follicle reached 14 mm or serum oestradiol level was ≥200 ng/mL. The median duration of stimulation, day of commencing pituitary suppression and duration of suppression were similar in both groups, with 8, 5, and 5 days, respectively. The median number of cumulus-oophorous complexes (4.0 vs 5.5), metaphase-two oocytes (3 vs 4), the total number of oocytes cryopreserved (3.0 vs 4.5), and oocyte maturation rates (0.67 vs 0.70) were similar between the fPPOS and GnRH-ant groups, respectively. There was one case of premature ovulation in the fPPOS group and none in the GnRH-ant group (

Research question Do live birth rates (LBR), obstetric and perinatal outcomes vary between women who underwent frozen embryo transfer (ET) in the immediately subsequent menstrual cycle, and with those who underwent delayed frozen ET. Design Retrospective cohort study (n = 198) consisting of 119 women who underwent immediate transfer within 30 days of oocyte retrieval (OR) and 79 women who underwent delayed transfer which was performed after >30 days following OR. Either flexible antagonist or flexible progestin-primed ovarian stimulation protocols were started after a baseline ultrasonography on the second or third day of menstrual cycle. Only freeze all cycles were included in the study and all transfers were with hormonal endometrial preparation. Main outcome measures were LBR, birth weight, gestational day at birth and pregnancy complications. Results Peak estradiol level on trigger day (2746 vs 2081 pg/ml) and number of metaphase-two oocytes (13 vs 10) were significantly higher in the immediate transfer group. Clinical pregnancy rate per ET was similar between the groups (50.4% vs 44.3%). However, miscarriage rate per positive pregnancy was significantly higher (12.3% vs 31.1%) while LBR per ET was significantly lower (42.9% vs 26.6%) in the delayed transfer group. Median gestational age at delivery were 267.5 and 268 days in the immediate and delayed transfer groups. Median birthweight was significantly higher in the delayed transfer group (3520 vs 3195 g). Adjusted analyses also suggest similar LBR with immediate and delayed transfer. Conclusion(s) Frozen ET in the immediate menstrual cycle and delayed ET, after a freeze all strategy did not show significant difference in terms of LBR after adjustment. Obstetric and perinatal outcomes of frozen ET in the immediate menstrual cycle appear reassuring.