Progestins for pituitary suppression during ovarian stimulation for ART: a comprehensive and systematic review including meta-analyses

2020 ◽  
Vol 27 (1) ◽  
pp. 48-66 ◽  
Author(s):  
Baris Ata ◽  
Martina Capuzzo ◽  
Engin Turkgeldi ◽  
Sule Yildiz ◽  
Antonio La Marca
Keyword(s):  
Live Birth ◽  
Gnrh Agonist ◽  
Ovarian Stimulation ◽  
Pregnancy Rates ◽  
Clinical Pregnancy ◽  
Sensitivity Analyses ◽  
Gnrh Analogue ◽  
Gnrh Analogues ◽  
Clinical Pregnancy Rates ◽  
Pituitary Suppression

Abstract BACKGROUND Progestins are capable of suppressing endogenous LH secretion from the pituitary. Progestins can be used orally and are less expensive than GnRH analogues. However, early endometrial exposure to progestin precludes a fresh embryo transfer (ET), but the advent of vitrification and increasing number of oocyte cryopreservation cycles allow more opportunities for using progestins for pituitary suppression. OBJECTIVE AND RATIONALE This review summarizes: the mechanism of pituitary suppression by progestins; the effectiveness of progestins when compared with GnRH analogues and with each other; the effect of progestins on oocyte and embryo developmental potential and euploidy status; and the cost-effectiveness aspects of progestin primed stimulation. Future research priorities are also identified. SEARCH METHODS The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed, the Web of Science and Scopus were screened with a combination of keywords related to ART, progesterone, GnRH analogue and ovarian stimulation, in various combinations. The search period was from the date of inception of each database until 1 April 2020. Only full text papers published in English were included. OUTCOMES Overall, the duration of stimulation, gonadotrophin consumption and oocyte yield were similar with progestins and GnRH analogues. However, sensitivity analyses suggested that progestins were associated with significantly lower gonadotrophin consumption than the long GnRH agonist protocol (mean difference (MD) = −648, 95% CI = −746 to −550 IU) and significantly higher gonadotrophin consumption than the short GnRH agonist protocol (MD = 433, 95% CI = 311 to 555 IU). Overall, live birth, ongoing and clinical pregnancy rates per ET were similar with progestins and GnRH analogues. However, when progestins were compared with GnRH agonists, sensitivity analyses including women with polycystic ovary syndrome (risk ratio (RR) = 1.27, 95% CI = 1.06 to 1.53) and short GnRH agonist protocols (RR = 1.14, 95% CI = 1.02 to 1.28) showed significantly higher clinical pregnancy rates with progestins. However, the quality of evidence is low. Studies comparing medroxyprogesterone acetate, dydrogesterone and micronized progesterone suggested similar ovarian response and pregnancy outcomes. The euploidy status of embryos from progestin primed cycles was similar to that of embryos from conventional stimulation cycles. Available information is reassuring regarding obstetric and neonatal outcomes with the use of progestins. Despite the lower cost of progestins than GnRH analogues, the mandatory cryopreservation of all embryos followed by a deferred transfer may increase cost per live birth with progestins as compared to an ART cycle culminating in a fresh ET. WIDER IMPLICATIONS Progestins can present an effective option for women who do not contemplate a fresh ET, e.g. fertility preservation, anticipated hyper responders, preimplantation genetic testing, oocyte donors, double stimulation cycles.

P–708 Comparison of reproductive outcomes after progestin-primed ovarian stimulation with dydrogesterone versus cetrorelix to inhibit spontaneous ovulation in oocyte donation

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
J A Moreno ◽  
P Masoli ◽  
C Sferrazza ◽  
H Leiva ◽  
O Espinosa ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Live Birth ◽  
Ovarian Stimulation ◽  
Fertilization Rate ◽  
Oocyte Donation ◽  
Pregnancy Rates ◽  
Clinical Pregnancy ◽  
Reproductive Outcomes ◽  
Ongoing Pregnancy ◽  
Live Births

Abstract Study question Is dydrogesterone (DYG) equivalent compared to cetrorelix with respect to clinical pregnancy rate, ongoing pregnancy rate and live birth rate in oocyte donation (OD) cycles? Summary answer DYG is comparable to cetrorelix in terms of clinical pregnancy, but higher rates of ongoing pregnancy and live birth were observed in the DYG group What is known already Progestin-primed ovarian stimulation (PPOS) is an ovarian stimulation regimen based on a freeze-all strategy using progestin as an alternative to GnRH analog for suppressing a premature LH surge. DYG is an oral progestin that has been studied in PPOS protocols. Published reports indicate that length of ovarian stimulation, dose of gonadotrophin needed and number of MII retrieved from PPOS cycles are comparable to short protocol of GnRH agonists during OD cycles. However, while some studies noted no differences in terms of live births, worse pregnancy rates have been reported in recipients of oocytes from PPOS cycles compared to GnRH antagonists. Study design, size, duration Prospective controlled study to assess the reproductive outcomes of OD recipients in which the donors were subjected to the DYG protocol (20mg/day) compared with those subjected to the short protocol with cetrorelix (0.25 mg/day) from Day 7 or since a leading follicle reached 14 mm. The OD cycles were triggered with triptoreline acetate and the trigger criterion was ≥3 follicles of diameter >18mm. Participants/materials, setting, methods 202 oocyte donors were included, 92 under DYG and 110 under cetrorelix. The study was performed in a private infertility center between January 2017 and December 2020. The main outcome included the rates of clinical pregnancy, ongoing pregnancy and live births. Secondary outcomes included the number of oocytes retrieved, number of MII, fertilization rate, length of stimulation and total gonadotropin dose. Differences were tested using a Student’s t-test or a Chi2 test, as appropriate. Main results and the role of chance Compared to antagonist cycles, cycles under DYG had fewer days of stimulation (9.9 ± 0.9 vs. 10.8 ± 1.1, p<.001) and a lower total gonadotropin dose (1654 ± 402.4 IU vs. 1844 ± 422 IU, p<.001). The number of MII retrieved was no different: 16.9 (SD 6.2) with DYG and 15.4 (SD 5.8) with cetrorelix (p = 0.072). Recipients and embryo transfer (ET) characteristics were also similar between groups. The mean number of MII assigned to each recipients was 6.7 (SD 1.8) in DYG and 6.6 (SD 1.7) in cetrorelix (P = 0.446). The fertilization rate was 66.2% in DYG versus 67.6% in cetrorelix (P = 0.68). Regarding the reproductive outcomes, the overall clinical pregnancy rate in DYG group (65/87: 74.7%) and cetrorelix group (66/104: 63.4%) (p = 0.118) was similar. Meanwhile, the DYG group compared to cetrorelix group had higher rates of ongoing pregnancy (63.2% vs 45.1%; p = 0.014) and live births (54,9% vs 37.8%; p = 0.040). Limitations, reasons for caution These results should be evaluated with caution. The limitations of this study include the limited number of participants enrolled and the limited data on pregnancy outcomes. A randomized controlled trial is necessary to provide more evidence on the efficacy of the DYG protocol. Wider implications of the findings: The efficacy of PPOS protocol compared to GnRH-antagonist protocol in terms of reproductive outcomes has been little studied. PPOS using DYG yields comparable clinical pregnancy rates compared to cetrorelix in OD cycles. The differences found regarding the rates of ongoing pregnancy and live births should be further investigated. Trial registration number Not applicable

The effect of repeated controlled ovarian stimulation cycles on the gamete and embryo development

Zygote ◽  
2019 ◽  
Vol 27 (05) ◽  
pp. 347-349 ◽  
Author(s):  
L.T. Paul ◽  
O. Atilan ◽  
P. Tulay
Keyword(s):  
Adverse Effect ◽  
Pregnancy Outcomes ◽  
Ovarian Stimulation ◽  
Ovarian Response ◽  
Fertilization Rate ◽  
Pregnancy Rates ◽  
Clinical Pregnancy ◽  
Controlled Ovarian Stimulation ◽  
Developmental Potential ◽  
Clinical Pregnancy Rates

SummaryThe aim of this study was to investigate if there is an adverse effect of multiple controlled ovarian stimulation (COS) on the maturity of oocytes (MI and MII), fertilization rate, embryo developmental qualities and clinical pregnancy rates in donation cycles. In total, 65 patients undergoing oocyte donation cycles multiple times were included in this study. Patients were grouped as group A that consisted of donors with ≤2 stimulation cycles while B consisted of donors with ≥3 stimulation cycles; and group C included donors who had ≤15 oocytes, while group D had donors with ≥16 oocytes. Numbers of oocytes obtained, MI and MII oocytes, fertilization, embryo quality and clinical pregnancy outcomes were compared. Significant statistical differences were observed in total number of oocytes obtained, maturity of oocytes (MI and MII), fertilization rate, embryo qualities and clinical pregnancy outcomes of donors in groups A–D. Donors with ≤2 ovarian stimulation cycles had lower numbers of immature oocytes than donors with three or more stimulation cycles. However, donors with ≥3 stimulation cycles had higher numbers of mature oocytes, zygotes, with better day 3 embryo qualities and higher clinical pregnancy rates than donors with ≤2 stimulation cycles. Repeated COS does not seem to have any adverse effect on ovarian response to higher dose of artificial gonadotropin, as quality of oocytes collected and their embryological developmental potential were not affected by the number of successive stimulation cycles. The effect of multiple COS on the health of the oocyte donor needs to be assessed for future purpose.

P–342 Are blastulation and clinical pregnancy rates in women with endometriomas different than those without?

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
R Kantarci ◽  
S Gule. Cekic ◽  
E Türkgeldi ◽  
S Yildiz ◽  
I Keles ◽  
...  
Keyword(s):  
Live Birth ◽  
Ovarian Stimulation ◽  
Oocyte Quality ◽  
Unexplained Infertility ◽  
Clinical Pregnancy ◽  
Pregnancy Test ◽  
Positive Pregnancy Test ◽  
Clinical Pregnancy Rates ◽  
Blastulation Rate ◽  
Metaphase Ii Oocytes

Abstract 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 < 0.01] and infertility duration in years [2 (1–2.6) vs 3 (2–5), p < 0.01] were significantly lower in EG. Number of retrieved oocytes [8 (5–12) vs 12 (7–15.8), p < 0.01)] and metaphase-II oocytes [6 (4–10) vs 8.5 (6–12), p < 0.01] were lower in EG group compared to CG group. However, blastulation rate per MII oocyte were similar between the EG and CG [(0.25 (0.20–0.41) vs 0.30 (0.14–0.50), respectively, p = 0.58]. Adjusted analysis for age and number of MII oocytes revealed similar finding. 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

Prolonged ovarian stimulation in ART cycles does not improve clinical pregnancy rates in poor responders

2002 ◽  
Vol 78 ◽  
pp. S49 ◽  
Author(s):  
William H Catherino ◽  
Mark Leondires ◽  
Jeffrey McKeeby ◽  
David Cruess ◽  
James H Segars ◽  
...  
Keyword(s):  
Ovarian Stimulation ◽  
Pregnancy Rates ◽  
Clinical Pregnancy ◽  
Poor Responders ◽  
Clinical Pregnancy Rates
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