Does letrozole (LZ) co-treatment during ovarian stimulation with gonadotropins for in IVF impact follicle recruitment, oocyte number and quality, embryo quality, or live birth rate (LBR)?

Progesterone plays a key role in implantation. Several studies reported that lower luteal progesterone levels might be related to decreased chances of pregnancy. This systematic review was conducted using appropriate key words, on MEDLINE, EMBASE, and the Cochrane Library, from 1990 up to March 2021 to assess if luteal serum progesterone levels are associated with ongoing pregnancy (OP) and live birth (LB) rates (primary outcomes) and miscarriage rate (secondary outcome), according to the number of corpora lutea (CLs). Overall 2,632 non-duplicate records were identified, of which 32 relevant studies were available for quantitative analysis. In artificial cycles with no CL, OP and LB rates were significantly decreased when the luteal progesterone level falls below a certain threshold (risk ratio [RR] 0.72; 95% confidence interval [CI] 0.62–0.84 and 0.73; 95% CI 0.59–0.90, respectively), while the miscarriage rate was increased (RR 1.48; 95% CI 1.17–1.86). In stimulated cycles with several CLs, the mean luteal progesterone level in the no OP and no LB groups was significantly lower than in the OP and LB groups [difference in means 68.8 (95% CI 45.6–92.0) and 272.4 (95% CI 10.8–533.9), ng/ml, respectively]. Monitoring luteal serum progesterone levels could help in individualizing progesterone administration to enhance OP and LB rates, especially in cycles without corpus luteum.

This retrospective study investigated whether mid-luteal serum progesterone concentrations are associated with live birth rates in women with WHO group II anovulatory infertility undergoing ovulation induction. Data were from women (n=335) stimulated with gonadotrophins using a low-dose step-up protocol, of which women with presumptive ovulation (n=279), defined as a mid-luteal progesterone concentration ⩾7.9ng/ml (⩾25nmol/l; range 7.9-194ng/ml) were included. Of the women with presumptive ovulation, 57 (20.4%) had a live birth and their serum mid-luteal progesterone concentration was significantly (P=0.016) higher than that of the non-live birth group. There were significant associations between the number of large (⩾15mm) and medium-sized follicles (12-14mm) at human chorionic gonadotrophin administration and the mid-luteal progesterone concentration (P<0.001), while the total number of large and medium-sized follicles was not significantly associated with live birth rate. In conclusion, mid-luteal progesterone concentrations above the cut-off values currently used for defining ovulation were positively associated with live birth rates in normogonadotrophic anovulatory women undergoing ovulation induction with gonadotrophins. The mid-luteal progesterone concentration, apart from being a consequence of the number of corpora lutea, may also reflect the quality of the follicle/oocyte/corpus luteum. Measurement of blood concentration of the steroid hormone progesterone in the mid-postovulatory phase of the menstrual cycle is frequently used to determine ovulation. The aim of this study was to investigate whether increasing blood concentrations of progesterone in the mid-postovulatory phase was associated with higher chances of achieving a live birth in a group of 335 women with anovulatory infertility, who had undergone stimulation with gonadotrophin hormones for the purpose of inducing ovulation. Statistical analysis, performed on the 279 women with presumptive ovulation (defined as a mid-postovulatory progesterone concentration ⩾7.9ng/ml serum), showed that the mid-postovulatory progesterone concentration was significantly positively associated with live birth rate. There was also a significant association between follicular development at end of gonadotrophin stimulation and the mid-postovulatory progesterone concentration, but follicular development could not explain live birth rate as mid-postovulatory progesterone concentrations could. In conclusion, increased blood concentrations of progesterone in the mid-postovulatory phase of the menstrual cycle above the threshold values currently used for defining ovulation were associated with increased live birth rates in anovulatory women undergoing ovulation induction with gonadotrophin hormones. The mid-postovulatory progesterone concentration, apart from being a consequence of the quantity of follicular development, may therefore also reflect the quality of the ovarian follicles and eggs. Copyright © 2011 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

The objective of this comparative study was to determine the influence of changes in estradiol and progesterone during ovulatory vs. anovulatory cycles on levels of estradiol receptor (ER) and progesterone receptor (PgR) in endometrium. Thirty women (range age 20-35 years) were divided into three groups: women with a history of habitual abortion, obese women with menstrual disorders, and women with regular ovulatory cycles as well as proven fertility. A single venous blood sample and an endometrial sample were simultaneously obtained during the secretory phase of the menstrual cycle, in order to measure estradiol and progesterone levels and ER and PgR concentrations in cytosol and salt-extracted nucleosol. Plasma estradiol levels were not different between groups. Plasma progesterone was two times higher in fertile women than in habitual aborters. In endometrial tissue, progesterone content was 200 times higher in fertile women than in habitual aborters. ER and PgR were lower in the cytosol than in the nuclear fraction in fertile and obese women. Both receptors were at their lowest level in the cytosol and nuclear compartment of women with recurrent miscarriage. Fluctuations mainly in the sex hormone progesterone, in plasma and endometrium tissue, could interfere with ER and PgR levels.

In women with threatened miscarriage, does progesterone supplementation until the completion of the first trimester of pregnancy increase the probability of live birth?

Can supplementation with rectal administration of progesterone secure high ongoing pregnancy rates (OPRs) in patients with low serum progesterone (P4) on the day of blastocyst transfer (ET)?

Only a small number of studies have reported the use of progesterone vaginal gel in combination with dydrogesterone as part of the antagonist protocol for fresh embryo transfer. Therefore, this study aimed to compare the effects of two types of luteal support on pregnancy outcomes following the antagonist protocol for fresh embryo transfer.

The aim of the present meta-analysis was to evaluate the effects of the addition of single-dose gonadotropin-releasing hormone agonist (GnRHa) for luteal support on pregnancy outcomes in females partaking in fertilization or intracytoplasmic sperm injection cycles. In total, the studies were hand-searched from six electronic databases to compare the pregnancy outcomes between single-dose GnRHa administered as luteal phase support (GnRHa group) and regular luteal support (control group). In the GnRHa group, single-dose GnRH agonist were administered at 5/6 days after IVF/ICSI procedures. In the control group, single-dose GnRH agonist was not added during luteal phase support. Only randomized controlled trials were included. Sensitivity analysis was performed using Revman 5.3 software; the high heterogeneity identified in the present analysis was primarily caused by one study included. Following exclusion of this particular study, the meta-analysis results indicated significantly higher rates of ongoing pregnancy or live birth per transfer (P=0.002), clinical pregnancy per transfer (CPR; P=0.001) and multiple pregnancy per pregnancy (P=0.020) in the GnRHa group compared with those in the control group. Meta-analysis of a subgroup of trials with long-acting GnRH-a ovarian treatment protocols indicated that the rate of ongoing pregnancy or live birth (P=0.080), CPR (P=0.090) and multiple pregnancy per pregnancy (P=0.140) were not significantly different between the two groups. However, the results from trials that had used a multi-dose GnRH antagonist ovarian treatment protocol indicated a significantly higher ongoing pregnancy or live birth rate per transfer (P=0.010), CPR per transfer (P<0.0001) and multiple pregnancy rate per pregnancy (P=0.003) compared with those in the control group. The present results suggested that administration of single-dose GnRH agonist in the luteal phase may be an ideal choice for patients undergoing IVF/ICSI therapy.Copyright © 2020, Spandidos Publications.

This pilot study investigates the role of luteal supplementation with recombinant LH in an attempt to reverse the poor reproductive outcome previously noticed after GnRH-agonist triggering of final oocyte maturation for IVF. Similar implantation rates were achieved with the novel recombinant LH luteal supplementation scheme compared with the standard luteal P protocol (25.0% vs. 26.7%, respectively). No cases of ovarian hyperstimulation syndrome (OHSS) were noticed in either group.Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Gonadotrophin releasing hormone (GnRH) agonist trigger after GnRH antagonist-based ovarian stimulation protocol for IVF is gaining popularity, because it prevents ovarian hyperstimulation syndrome and allows for near physiological LH and FSH surges. A small dose of HCG (1500 IU) on the day of oocyte retrieval, followed by daily progesterone administration, is currently the preferred way to secure adequate luteal support after GnRH agonist trigger. In the present study, the possibility that a bolus of 1500 IU HCG, given 2 days after oocyte retrieval, may be sufficient to sustain adequate luteal support without additional progesterone treatment was questioned.A non-interventional retrospective cohort study between conducted between April 2017 and August 2018. A total of 154 consecutive patients treated with GnRH agonist trigger followed by day-2 HCG (1500 IU) support only (study group) were included. Data were compared with 155 consecutive patients who were treated with HCG (6500 IU) trigger followed by conventional progesterone luteal support (control group).Pregnancy, miscarriage and live birth rates were comparable between the study and control groups. In patients who became pregnant, mean oestradiol level 14 days after oocyte retrieval was 4719 pmol/l and 2672 pmol/l in the study and control group, respectively (P < 0.001), reflecting robust luteal activity in the study group.A bolus of 1500 IU HCG, administered 2 days after retrieval, can provide excellent luteal support, without the need for further progesterone supplementation.Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Preterm birth (PTB) is an important cause of neonatal mortality and morbidity. Spontaneous PTB (sPTB) is the most common cause of PTB. In patients with a singleton pregnancy, progesterone treatment appears to reduce the rate of spontaneous preterm birth in those with a previous history of spontaneous preterm labor and/or cervical shortening in the current pregnancy. Progesterone therapies used for the prevention of sPTB may increase the risk of gestational diabetes mellitus (GDM) towards the end of pregnancy owing to their effects on carbohydrate metabolism.We aimed to show the effects of vaginal progesterone use, starting time, and duration of treatment on GDM.A retrospective cohort study was carried out in pregnant women 18 to 39 years old who came to our hospital between January 1, 2021, and August 31, 2021, and who had a 2-hour 75-g oral glucose tolerance test (OGTT) at 24 to 28 weeks of gestation. In a total of 540 patients, 68 were diagnosed with GDM based on at least one abnormal plasma glucose value at screening. The remaining 472 patients with normal plasma glucose levels were considered as the control group. The groups were compared in terms of age, parity, pre-pregnancy body mass index (BMI), smoking, gestational age, and vaginal progesterone use. Patients using vaginal progesterone with and without GDM were then compared again in terms of indications for vaginal progesterone use, initiation time of progesterone therapy, duration of progesterone use, and cervical length.The incidence of GDM in our study group was 12.5%. Despite the use of vaginal progesterone at a higher rate in the GDM group than in the control group (23.5 vs. 13.9%; p=0.07), it was not statistically significant. When we examined patients using progesterone as a subgroup analysis, the mean time to start vaginal progesterone treatment was 19.8±2.6 (14-24), and it was significantly earlier in the GDM group (18.1±2.0 vs. 20.2±2.6; p=0.007). Initiation of vaginal progesterone before 20 weeks of gestation was statistically significantly more frequent in the GDM group than the control group (68.8 vs. 39.4%; p=0.050 OR :3.3, 95%CI: 1.0-10.8). The mean duration of vaginal progesterone use was 50.0±15.6 days (28-90) and it was longer in the GDM group (57.8±13.4 vs. 48.1±15.6; p=0.027).Since the duration of vaginal progesterone use will be prolonged, there may be a risk of GDM, especially in patients who started vaginal progesterone before the 20th week of pregnancy. Even if the OGTT test performed between 24-28 weeks is normal, it should be kept in mind that these patients may have GDM in the later weeks of pregnancy, and repeating the OGTT test should be considered if necessary.Thieme. All rights reserved.