Random-start Ovarian Stimulation Research Articles

Trends and Regional Differences for Fertility Preservation Procedures in Women With Breast Cancer

IntroductionBreast cancer is the most common malignancy in women of reproductive age and chemotherapy protocols impair fertility, frequently necessitating fertility preservation (FP) referral. Embryo, oocyte, or ovarian tissue cryopreservation are established FP modalities in women with breast cancer but there are few data on their uptake over time. In this study our aim was to determine the regional time trends and utility differences for fertility preservation methods of reproductive tissue cryopreservation. MethodsThis multicenter study included 1623 women diagnosed with breast cancer from 7 tertiary centers in 6 countries (Brazil, Italy, Scotland, South Korea, Turkey, USA). Participant centers provided the details of FP cryopreservation approaches broken down annually from 2012 to 2021. Women with newly diagnosed breast cancer, aged 18-45 years who were referred for FP at participating centers and had normal ovarian function at the time were included. ResultsWe found a mean increase of 7% per year (P = .002, adjusting for centers) in the number of women referred for FP. Of those who were referred (n = 1623), a mean 38.7% underwent FP (n = 629), with a range of 12% in South Korea) to 95% in Brazil. The number of women undergoing ovarian stimulation for FP continually increased until 2021, with oocyte cryopreservation being the most common procedure throughout the study period (P = .014 for time trend). The proportion of random start ovarian stimulation cycles increased each year from 58.3% in 2012 to 86.8% in 2021, (P = .005 for time trend, and P = .04 for 2012 vs. 2021). ConclusionsThe utility of FP has steadily increased for young women with breast cancer over the last decade, although regional differences significantly influence FP practices. The findings of our study could have value for policy making in FP care for young women with breast cancer at the local, regional, or global level.

Undetected, natural conception pregnancies in luteal phase stimulations-case series and review of literature.

What is the risk of an undetected natural conception pregnancy during luteal phase ovarian stimulation, and how does it impact the pregnancy's course? The risk for an undetected, natural conception pregnancy in luteal phase ovarian stimulation is low and it appears that ovarian stimulation is unlikely to harm the pregnancy. Random start ovarian stimulation appears to be similarly effective as early follicular stimulation start; and it allows ovarian stimulation to be started independent of the cycle day and throughout the cycle, in accordance with the patients' and clinics' schedule as long as there is no intention of a fresh embryo transfer in the same cycle. Starting ovarian stimulation in the luteal phase bears the possibility of an-at the timepoint of stimulation start-undetected, natural conception pregnancy that has already occurred. There is scarce data on the incidence of this event as well as on the possible implications of ovarian stimulation on the course of an existing pregnancy. This retrospective observational study, performed between June 2017 and January 2024, analyzed luteal phase stimulations, in which a natural conception pregnancy was detected during the ovarian stimulation treatment for IVF/ICSI. Luteal phase stimulation was defined as ovarian stimulation started after ovulation and before the next expected menstrual bleeding, with a serum progesterone (P4) level of >1.5 ng/ml on the day of stimulation start or 1 day before. Women who underwent a luteal phase ovarian stimulation in a tertiary referral ART center. A total of 488 luteal phase stimulation cycles were included in the analysis. Luteal phase stimulation was only started after a negative serum hCG measurement on the day or 1 day before commencement of ovarian stimulation. Ten patients (2.1%) had an undetected natural conception pregnancy at the time of luteal phase stimulation start. Eight of these patients underwent an ovarian stimulation in a GnRH-antagonist protocol and two in a progestin-primed stimulation protocol (PPOS). Recombinant FSH was used as stimulation medication for all patients, the patients with a PPOS protocol received additional recombinant LH. One pregnancy (0.2%) was detected after the oocyte retrieval, the other nine pregnancies were detected either due to persistent high serum progesterone levels or due to an increasing progesterone level after an initial decrease before oocyte retrieval. In the cycles with an undetected natural conception pregnancy, the median number of stimulation days was 8 days (range: 6-11 days) and median serum hCG at detection of pregnancy was 59 IU hCG (range: 14.91-183.1). From 10 patients with a pregnancy, three patients delivered a healthy baby, two patients had ongoing pregnancies at the time of summarizing the data, three patients had biochemical pregnancies (patient age: 30, 39, and 42 years), one patient had an ectopic pregnancy which required a salpingectomy, and one patient (age: 34 years) had an early pregnancy loss. The retrospective study design and the small sample size can limit the accuracy of the estimates. Overall, there is a small risk of undetected natural conception pregnancies when luteal phase stimulation is undertaken. It appears that there are no adverse effects through either direct effect on the embryo or indirectly through a detrimental effect on the corpus luteum function on the pregnancy in our cohort. This study did not receive funding. The authors declare that there is no conflict of interest. N/A.

The dark side of random-start ovarian stimulation: ovarian hyperstimulation syndrome due to inadvertent pregnancy

Research QuestionCan inadvertent pregnancies go unnoticed when initiating random-start ovarian stimulation (RSOS) despite monitoring? DesignCase series at the university-based tertiary-care fertility clinic. ResultsBetween June 2022 and December 2023, two cases of undetected early pregnancy at the onset of random-start ovarian stimulation were identified, both leading to severe ovarian hyperstimulation syndrome (OHSS) with hospitalization. ConclusionRSOS protocols add flexibility in fertility clinics when there is no intention of a fresh embryo transfer but may be associated with insidious risk of OHSS. We advocate for comprehensive consultation and serial monitoring of human chorionic gonadotropin (hCG) during stimulation while cautioning against overreliance on baseline hormone levels when initiating RSOS. If the benefits of RSOS seem limited, healthcare providers should consider delaying the stimulation to avert health, but also medicolegal, and financial complications.

Random-start ovarian stimulation in an oocyte donation programme: a large, single-centre, experience

Research questionDo live birth rates differ between recipients matched with donors using conventional ovarian stimulation compared with those using random-start protocols? DesignRetrospective analysis of 891 ovarian stimulations in egg donors (January–December 2018) and clinical outcomes in matched recipients (n = 935). Donors commenced ovarian stimulation on day 1–3 of the menstrual cycle (n = 223) or in the mid/late-follicular (n = 388) or luteal phase (n = 280) under a conventional antagonist protocol. Live birth rate of matched recipients was the main outcome. ResultsDuration of stimulation and total gonadotrophin dose were comparable between conventional versus random-start groups. The number of collected eggs were similar (17.6 ± 8.8 versus 17.2 ± 8.5, P = 0.6, respectively). Sub-group analysis showed that stimulation length (10.2 ± 1.8 versus 9.8 ± 1.7 versus 10.4 ± 1.7, P < 0.001) and gonadotrophin consumption (2041.5 ± 645.3 versus 2003.2 ± 647.3 versus 2158.2 ± 685.7 IU, P = 0.01) differed significantly between the conventional, mid/late follicular and luteal phase groups, respectively. In matched recipients receiving fresh oocytes and undergoing fresh embryo transfer, the biochemical pregnancy (63.8% and 63.3%; P = 0.9), clinical pregnancy (54.6% and 56.1%; P = 0.8) and live birth rates (47.7% and 46.6%; P = 0.7) per embryo-transfer were similar between conventional versus random groups. Similar results were obtained in recipients receiving vitrified eggs. Euploidy rate was also comparable. ConclusionsNo notable variations were found in clinical outcomes using oocytes obtained from random-start protocols and those proceeding from conventional ovarian stimulation in oocyte donation treatments. Luteal-phase stimulation seems to require longer stimulation and higher FSH consumption. Random-start stimulation strategy does not impair the potential of the oocyte yield or clinical outcomes in oocyte donation cycles.

OUTCOMES FOLLOWING RANDOM START PLUS PROGESTIN PRIMED OVARIAN STIMULATION IN AN OOCYTE DONATION PROGRAM

Random-start ovarian stimulation protocols have emerged allowing treatment to begin at any day of the menstrual cycle. Concomitantly, in what is called progestin primed oocyte stimulation (PPOS), the use of progestins seem similarly as effective as GnRH antagonists in preventing LH surge. If ovarian stimulation can be initiated randomly together with the advantages of PPOS, without adversely impacting oocyte yield or quality, the approach may facilitate tasks in oocyte donation (OD) units.

Clinical outcome of embryo cryopreservation in Japanese breast cancer patients: pregnancy rates after transfer of thawed embryos.

To examine pregnancy outcomes after cryopreserved embryo transfer (ET) in breast cancer patients and to investigate the effect of controlled ovarian hyperstimulation (COH) as well as that of aromatase inhibitor (AI) administration and of the random start (RS) ovarian stimulation method. This retrospective study covered 126 patients who underwent embryo cryopreservation between 2010 and 2019. Thirty-one patients underwent frozen embryo transfer (FET), and we examined resulting pregnancy rates (PRs) and live birth rates (LBRs) in those who did and did not undergo COH and in relation to the AI and RS methods. PR and LBR per patient were higher among patients who underwent COH than among those who did not. PR per ET did not differ from that documented for non-cancer infertility patients, after adjustment for age. The PR and LBR did not differ between use and non-use of AI (27.8% vs 35.2%). In addition, there was no significant difference in the PR or LBR between RS and conventional start ovarian stimulation (33.3% vs 30.8%). No prenatal fetal abnormalities were observed in 8 cases (including 5 AI cases and 2 RS cases). This study showed that the outcome of FET after FP was equivalent to that seen in non-cancer patients. Further, neither use of AI nor the RS method influenced LBR. COH including use of AI and the RS method are useful in FP for collecting and freezing many embryos within a short period and for increasing the per patient LBR after cancer treatment.

Usefulness of random-start progestin-primed ovarian stimulation for fertility preservation

BackgroundProgestin-primed ovarian stimulation (PPOS) has been used in infertility cases in recent years, and several reports have stated that it has oocyte collection results similar to those of gonadotropin-releasing hormone antagonist (GnRH-ant) protocol. For emergency fertility preservation, random-start ovarian stimulation is usually recommended. Therefore we compared the clinical outcomes of random-start PPOS with those of conventional random-start GnRH-ant protocols in fertility-preserving cases.MethodsWe retrospectively examined 86 cycles of oocyte collection, of which 56 were random-start GnRH-ant and 30 were random-start PPOS for fertility preservation at our hospital between January 2016 and April 2021. The primary outcome was the number of mature oocytes per cycle. The secondary outcome was the number of vitrified blastocysts per cycle for embryo freezing cases.ResultsNo significant differences were noted in the number of days of stimulation, total dose of gonadotropin preparation, and the number of mature oocytes and vitrified blastocysts. The number of hospital visits for monitoring was significantly lower in the PPOS group. The start of menstruation before oocyte collection was significantly less in the PPOS group.ConclusionsRandom-start PPOS and GnRH-ant were similar in oocyte collection results. PPOS can reduce the number of hospital visits, thus reducing patient stress. PPOS at the start of the luteal phase can prevent the start of menstruation during ovarian stimulation.

O-112 Outcomes of random-start ovarian stimulation protocols as a possible evidence of the theory of antral follicles continuous recruitment

Abstract Study question We tried to validate the possibility and efficiency of ovarian stimulation (OS) started on any day of the menstrual cycle, based on a theory of continuous recruitment of antral follicles. Summary answer Formation of a pool of follicles with higher sensitivity to gonadotropic stimulation occurs several times during the menstrual cycle (MC). What is known already According to classical concepts and fundamental positions formulated in the middle of the last century, follicular recruitment occurs only once during the menstrual cycle - in the early follicular phase. Nowadays there is increasing evidence to suggest that there are multiple (two or three) antral follicular waves of recruitment during the MC. Also some researchers state that the process of follicle recruitment is continuous. Study design, size, duration This prospective clinical study was conducted at the V.I. Kulakov NMRC for OG&amp;Pof Russia. The study included female cancer patients seeking retrieval and cryopreservation of oocytes and/or embryos before cancer treatment. 240 patients were selected for the study. The patients were divided into 5 groups depending on the cycle day on the moment when ovarian stimulation was initiated. All patients signed an informed consent form approved by the Ethics Committee. Participants/materials, setting, methods The 1st group consisted of patients who started standart OS from 1 to 5 days of the cycle (n = 65); the 2nd - from 6 to 10 (n = 36), the 3rd - from 11 to 15 (n = 45), the 4th - from 16 to 22 (n = 44), the 5th - from 23 to 28 (n = 50). In the late follicular and luteal phase we performed OS without a pituitary modulator. The comparative analysis included features of oo-, embryogenesis and steroidogenesis. Main results and the role of chance The mean age, BMI and AMH were not different among groups. There were no LH rise or OHSS signs noticed in any groups, despite that OS in late follicular and luteal phase of the MC was performed with no GnRH antagonist addition.There was no statistically significant difference in the duration of stimulation, starting doses, total dose of FSH and HMG. The largest number of oocyte cumulus complexes was obtained in the 5th group (11 (9–21) vs 7 (3,5–15,5) in the 1st group, p = 0,030). The greatest number of mature oocytes was obtained in the 4th and 1st groups. In the 2nd group the largest number of immature oocytes was obtained (37 (9.1%)). A smaller number of mature oocytes (165 (61.8%) vs 492 (72.9%) and 314 (77.5%), p = 0.001) was obtained in group 2 (compared with the 1st and the 4th groups), when stimulation was started in the presence of a dominant follicle . These periods coincided with higher estradiol and lower FSH serum levels. Based on our data the optimal moment for effective OS initiation starts with the decrease in serum estradiol which is approximately 48 hours before the menstrual bleeding. Limitations, reasons for caution The presented results could be applied mainly to young patients with high and normal ovarian reserve, who were in the main study group. In patients with low ovarian reserve, short menstrual cycle and early ovulation an issue of favorable time points for the initiation of OS should be resolved individually. Wider implications of the findings The data collected during our research could possibly contribute to future personification of OS protocols. Tailoring the ovarian stimulation protocols to the needs of the patients could decrease time needed for completing the protocol without affecting oocyte yield or their maturity. Trial registration number none

How effective are the non-conventional ovarian stimulation protocols in ART? A systematic review and meta-analysis.

To compare the effectiveness of starting the ovarian stimulation on the early follicular phase ("Conventional") with the newer range of non-conventional approaches starting in the luteal phase ("Luteal"), random-start, and studies implementing them in DuoStim ("Conventional"+"Luteal"). Systematic review. We searched CENTRAL, PubMed, and Embase, on March 2020. We included randomized and non-randomized controlled trials that compared "Luteal," random-start ovarian stimulation or DuoStim with "Conventional"; we analyzed them by subgroups: oocyte freezing and patients undergoing ART treatments, both, in the general infertile population and among poor responders. The following results come from a sensitivity analysis that included only the low/moderate risk of bias studies. When comparing "Luteal" to "Conventional," clinically relevant differences in MII oocytes were ruled out in all subgroups. We found that "Luteal" probably increases the COH length both, in the general infertile population (OR 2.00days, 95% CI 0.81 to 3.19, moderate-quality evidence) and in oocyte freezing cycles (MD 0.85days, 95% CI 0.53 to 1.18, moderate-quality evidence). When analyzing DuoStim among poor responders, we found that it appears to generate a higher number of MII oocytes in comparison with a single "Conventional" (MD 3.35, 95%CI 2.54-4.15, moderate-quality evidence). Overall, this systematic review of the available data demonstrates that in poor responders, general infertile population and oocyte freezing for cancer stimulation in the late follicular and luteal phases can be utilized in non-conventional approaches such as random-start and DuoStim cycles, offering similar outcomes to the conventional cycles but potentially with increased flexibility, within a reduced time frame. However, more well-designed trials are required to establish certainty.

THE USE OF DYDROGESTERONE TO PREVENT LH PEAK IN RANDOM-START OVARIAN STIMULATION FOR FERTILITY PRESERVATION

Compare the efficacy of oral dydrogesterone to prevent LH peak during ovarian stimulation versus usual antagonist protocol in fertility preservation cases with oocyte vitrification. Randomized prospective study from August 2019 to March 2020 at the Gynecology, Obstetric and Reproductive Medicine department of the Aziza Othmana University Hospital. Inclusion criteria: All patients underwent controlled ovarian stimulation for fertility preservation via oocyte vitrification. Exclusion criteria: Patients with hormone-dependent diseases (breast cancer, systemic lupus). Random-start ovarian stimulation was conducted with 300 IU of recombinant FSH for all patients. Patients were randomized into 2 groups on the day of the onset of ovarian stimulation: Group 1: prevention of LH peak using Dydrogesterone orally: 10 mg three times a day; beginning the first day of ovarian stimulation. Group 2: Prevention of LH peak by subcutaneous injection of Cetrotelix 0.25 mg per day from the first day of ovarian stimulation. Ovulation was triggered with 0.2 mg triptoreline. Oocyte pickup took place 37 hours later, either vaginally or per urethral transvesical route (for virgin patients). χ2 test was used to compare qualitative variables. Student’s t-test was used to compare quantitative variables. P-value < 0.05 was considered as statistically significant. Forty-seven patients were included in our study: 22 in Group 1 and 25 in Group 2. There was no significant difference regarding the clinical characteristics of the 2 groups (Group 1 vs Group 2) in terms of age (23.14 ± 5.07 vs 23.8 ± 5.7 , p: 0.7), BMI (21.63 ± 3.6 vs 22.48 ± 4.03 , p: 0.5), AMH levels (2.04 ± 1.24 vs 3.3 ± 1.93, p: 0.06), the duration of ovarian stimulation ( 9.14 ± 1.55 vs 9.33 ± 1.79 , p: 0.5), the number of follicles with a diameter > 15 mm on the day of triggering ( 7.62 ± 4.1 vs 7.5 ± 3.3, p: 0.6) and plasma oestrogen levels on the day of triggering ovulation (2587 ± 1601 vs 2083 ± 1163, p: 0.1) Moreover, pickup results were similar (goupe 1 vs group 2) for the number of CCOS( 12.71 ± 7.7 vs 12.29 ± 7.6 , p: 0.3) and the number of mature oocytes ( 9.85 ± 5.9 vs 9 ± 6.7 , p: 0.9). It should be noted that LH monitoring was performed in all patients and the difference was not significant either. Prevention of premature LH peak during COS is possible using dydrogesterone in Random-start protocols for fertility preservation, excluding cases of hormone-dependant diseases.

Ovarian stimulation in cancer patients: random versus conventional start

To determine if random start ovarian stimulation in cancer patients provides similar results compared to conventional stimulation starting in follicular phase. Retrospective data analysis at a single center (CEGYR). All patients undergoing oocyte cryopreservation for fertility preservation due to recent cancer diagnosis were rewied from 2012 to 2018. Patients were grouped according to random start or conventional start of the ovarian stimulation. Conventional start was defined as scheduled in early follicular phase initiation of gonadotrophins; random start was initiated at any other moment of the menstrual cycle. The analyzed variables were: number of oocytes, number of matured oocytes (metaphase II), and cycle length. 71 cycles met inclusion criteria. Oocytes were collected of 23 (33%) patients on the random start group and 48 (67%) from the conventional one. Mean age was 33.8 years old in the conventional and 33.25 years old in the random start groups. (p:0.65 IC95%, 2.04-3.23). The mean number of oocytes collected were similar 11.9 (conventional) versus 10.4 (random) (p:0.47 IC95%, 2.65-5.66) and mean number of mature oocytes vitrified was also similar (metaphase II): 9.30 (conventional) vs 7.6 (random) (p:0.34 IC95%, 1.81-5.13). The cycle duration was different, being the conventional shorter (9.7 days) than the random group (11.3 days) (p:0.0019 IC95%, 0.61-2.58). Random start stimulation cycles for cancer patients has comparable results and allows patients to start gonadotrophin stimulation irrespective of menstrual cycle phase, with no impairment of oocyte yield and only a small increase of cycle duration.

Back-to-back random-start ovarian stimulation prior to chemotherapy to maximize oocyte yield.

To evaluate the feasibility of utilizing back-to-back random-start ovarian stimulation to increase oocyte yield for fertility preservation prior to cancer treatment. A case series of 15 patients who underwent back-to-back random-start stimulation cycles prior to chemotherapy. Of the 15 back-to-back random-start stimulation cases, 13 had breast cancer and 2 had other cancers. The average age was 38years (range 30-43) and average AFC was 8 (range 3-14). Fourteen of the 15 women (93%) who underwent two ovarian stimulation cycles completed both of them. The average time to complete back-to-back random-start ovarian stimulation was 33days (range 13-43days). The average time between the first cycle completion and the second cycle start in our back-to-back random-start stimulations was 9days (range 0-14days). Two of the women underwent back-to-back random-start ovarian stimulation prior to starting neoadjuvant chemotherapy for breast cancer. Eleven of our 15 women at least doubled their oocyte or embryo yield relative to their first cycle. Only 1 of the 15 second cycles was canceled. The mature oocyte rate, fertilization rate, and embryo yield were similar among the first and second cycles. Back-to-back random-start ovarian stimulation may be an effective way to maximize fertility preservation, even in time-limited settings.

Random-start ovarian stimulation with aromatase inhibitor for fertility preservation in women with Japanese breast cancer.

PurposeFertility preservation is an important issue for young cancer patients. Random‐start controlled ovarian stimulation and double ovarian stimulation have been proposed for efficient oocyte retrieval within the limited time before cancer therapy. We aimed to clarify the efficacy of these new protocols within the Japanese population.MethodsWe performed a retrospective observational study at a multicenter from February 2012 to August 2017. The study entailed 50 cycles with 34 patients who underwent fertility preservation due to breast cancer. Follicular phase or luteal phase ovarian stimulation with aromatase inhibitor was performed. A second ovarian stimulation was started with or without waiting until the next menstruation. We measured the number of retrieved oocytes and cryopreserved oocytes/embryos, the ratio of mature oocytes, and the fertilization rate.ResultsThe numbers of retrieved oocytes and frozen oocytes/embryos were not significantly different between follicular phase and luteal phase ovarian stimulation. The number of retrieved oocytes was not reduced at the second ovum pick up compared to the first ovum pick up in the double ovarian stimulation.ConclusionsRandom‐start controlled ovarian stimulation and double ovarian stimulation with aromatase inhibitor for breast cancer patients were effective protocols for retrieving a greater number of oocytes within the limited time.

Specific protocols of controlled ovarian stimulation for oocyte cryopreservation in breast cancer patients.

Fertility preservation is an important concern in breast cancer patients. In the present investigation, we set out to create a specific protocol of controlled ovarian stimulation (cos) for oocyte cryopreservation in breast cancer patients. From November 2014 to December 2016, 109 patients were studied. The patients were assigned to a specific random-start ovarian stimulation protocol for oocyte cryopreservation. The endpoints were the numbers of oocytes retrieved and of mature oocytes cryopreserved, the total number of days of ovarian stimulation, the total dose of gonadotropin administered, and the estradiol level on the day of the trigger. Mean age in this cohort was 31.27 ± 4.23 years. The average duration of cos was 10.0 ± 1.39 days. The mean number of oocytes collected was 11.62 ± 7.96 and the mean number of vitrified oocytes was 9.60 ± 6.87. The mean estradiol concentration on triggering day was 706.30 ± 450.48 pg/mL, and the mean dose of gonadotropins administered was 2610.00 ± 716.51 IU. When comparing outcomes by phase of the cycle in which cos was commenced, we observed no significant differences in the numbers of oocytes collected and vitrified, the length of ovarian stimulation, and the estradiol level on trigger day. The total dose of follicle-stimulating hormone and human menopausal gonadotropin administered was statistically greater in the group starting cos in the luteal phase than in the group starting in the late follicular phase. Our results suggest that using a specific protocol with random-start ovarian stimulation for oocyte cryopreservation in breast cancer patients is effective and could be offered to young women undergoing oncologic treatment.

Random-start ovarian stimulation does not negatively impact egg yield/quality and produces high quality embryos in cancer patients

Since 2011, we have been initiating ovarian stimulation (random-start), at the time of the initial fertility preservation (FP) consultation, to minimize delays in cancer treatment. In this study, we aim to determine if random-start controlled ovarian stimulation (COS) is an effective method for FP, and if starting stimulation during a particular phase in the menstrual yields different results. Retrospective cohort. From 6/2011 to 3/2018, 1120 cancer patients were referred to our clinic for FP. All referred patients with no prior chemotherapy treatment, who underwent emergent FP treatment with an antagonist protocol, were included. Three hundred and eight patients met the inclusion criteria, with a total of 110 cycles initiated in the early follicular phase and 150 and 106 cycles initiated during the late follicular and luteal phases, respectively. ANOVA, T test and descriptive statistics were used to analyze the data as appropriate. There was no difference in age, BMI and AFC across the groups. Number of dominant follicles (≥13mm) on the day of trigger, mature oocytes retrieved, maturity rate (MII/total oocyte ratio) and mature oocyte yield (MII/AFC ratio) were similar across the groups (Table). There were significantly higher fertilization rates in random-start COS cycles compared to early follicular start. Additionally, number of high quality embryos frozen on Day 3 per MII oocyte retrieved was significantly higher in random-start cycles compared with early follicular start. The peak estradiol levels per mature follicle measured was significantly lower in random-start COS cycles. Ovarian Stimulation throughout the menstrual cycle yields similar oocyte maturity/developmental competence and high quality embryos. To minimize delays in cancer treatment, random-start COS should be considered the standard of care for patients undergoing emergent FP.Tabled 1Comparison between early, late follicular and luteal phase COS; means (SEM). NS: not significant.Oocyte & Embryo CryopreservationEarly Follicular Start (n=110)Late Follicular Start (n=150)Luteal Start (n=106)p valueTotal Stim Dose3594 (112)3817 (97)4191 (128)0.0016Days of Stim9.8 (0.2)10.2 (0.1)10.8 (0.2)<0.001Follicles ≥ 13 mm12.9 (0.7)14.0 (0.7)14.6 (0.8)NSMature Oocytes (MII) Retrieved12.3 (0.7)12.3 (0.8)12.8 (0.9)NSMII Oocyte / Total Oocyte Ratio0.75 (0.03)0.73 (0.02)0.74 (0.02)NSMII Oocyte / AFC Ratio0.98 (0.06)1.00 (0.07)0.99 (0.06)NSOocyte & Embryo Cryopreservation w/out LetrozoleEarly Follicular Start (n=40)Late Follicular Start (n=63)Luteal Start (n=41)p valueEstradiol / Follicles ≥ 13 mm216 (18)212 (10)168 (10)0.0175Embryo CryopreservationEarly Follicular Start (n=62)Late Follicular Start (n=54)Luteal Start (n=46)p valueFertilization Rate (2PN/MII)0.72 (0.03)0.84 (0.04)0.87 (0.03)0.0034Frozen Embryos / MII Oocyte0.60 (0.03)0.75 (0.05)0.81 (0.03)0.0008 Open table in a new tab

Random Start Ovarian Stimulation for Oocyte or Embryo Cryopreservation in Women Desiring Fertility Preservation Prior to Gonadotoxic Cancer Therapy.

Women of reproductive age diagnosed with cancer are often interested in preserving gametes or reproductive tissue that would allow for future genetic parenthood. Preservation of fertility is often accomplished in young cancer patients via ovarian stimulation followed by oocyte or embryo cryopreservation. Conventional stimulation protocols, however, require 2-4 weeks to complete ovarian stimulation, oocyte retrieval and possible fertilization. Such a strategy may not be feasible in patients requiring urgent cancer treatment. Recent studies have highlighted that random start ovarian stimulation can be initiated irrespective of the phase of the menstrual cycle and is an attractive alternative to conventional ovarian stimulation. The primary aim of the current review is to discuss the feasibility and success of random start ovarian stimulation for oocyte or embryo cryopreservation in women desiring fertility preservation prior to gonadotoxic cancer therapy. We performed a systematic review of medical literature published between January 2000 to June 2017 reporting the utility of random start ovarian stimulation for fertility preservation. Search terms included "fertility preservation," "cancer," "ovarian stimulation," "random-start ovarian stimulation," "embryo cryopreservation, and" "oocyte cryopreservation." Publications were included in this review only if patients underwent random start ovarian stimulation prior to cancer therapy. Nineteen publications were identified and perused by the authors. Most publications described the utility of random start ovarian stimulation in the setting of breast cancer. Radom-start stimulation was associated with a reduced time interval between ovarian stimulation initiation and oocyte or embryo cryopreservation. The yield of mature oocytes and their developmental potential into embryos was comparable between conventional and random-start protocols, albeit with higher gonadotropin doses in the latter. The current review suggests that random start ovarian stimulation can shorten the interval between ovarian stimulation and oocyte retrieval, with the yield of oocytes and embryos being comparable to conventional stimulation protocols. Thus, random start ovarian stimulation may serve as a better option for fertility preservation in patients requiring urgent cancer treatment.

Random start ovarian stimulation for fertility preservation appears unlikely to delay initiation of neoadjuvant chemotherapy for breast cancer.

Is random start ovarian stimulation associated with delays in initiation of neoadjuvant chemotherapy for breast cancer? Among women who complete fertility preservation (FP) consultation, random start ovarian stimulation is unlikely to delay time to initiation of neoadjuvant chemotherapy start. Neoadjuvant chemotherapy is now a widely accepted treatment modality for operable breast cancer and random start ovarian stimulation is an increasingly-utilized modality for FP. While conventional ovarian stimulation does not appear to delay starting adjuvant chemotherapy, the relationship between random start ovarian stimulation and neoadjuvant chemotherapy start is not well-understood. Cross-sectional study of all women seen between from January 2011 to April 2017 for FP consultation prior to starting neoadjuvant chemotherapy for breast cancer. A chart-review was performed. Study inclusion criteria were female sex; age 18-45; non-metastatic breast cancer diagnosis; underwent FP consultation; underwent neoadjuvant chemotherapy. Referrals for FP evaluation came from a regional referral base of oncology clinics. Various time-points related to cancer diagnosis, FP or chemotherapy were obtained from medical record review. We compared time-points between those who underwent ovarian stimulation for FP versus those who did not using T-tests and linear modeling. A total of 89 women who had FP consultation prior to neoadjuvant chemotherapy were identified. Sixty-seven percent underwent ovarian stimulation prior to cancer treatment and 33% did not. Women who underwent ovarian stimulation were similar in parity and clinical cancer stage to those who did not. Overall, the average time from cancer diagnosis to chemotherapy start was similar between the group that did undergo ovarian stimulation and those who did not (38.1 ± 11.3 versus 39.4 ± 18.5 days, P = 0.672). Those that underwent ovarian stimulation were referred 9.4 ± 6.8 days after diagnosis versus 17.9 ± 15.3 days for those who did not undergo ovarian stimulation (P < 0.001). Retrospective study with potential for selection bias among those who underwent ovarian stimulation versus those who did not. Reasons for caution include the possibility of unmeasured differences among those who did and did not undergo ovarian stimulation, including: patients' and providers' perceptions of the urgency to start chemotherapy, ongoing oncology work-up and treatment planning, FP decision-making, and the pursuit of second and third opinions. The difference in time from referral to FP consultation may have also influenced patients' decisions about whether to undergo ovarian stimulation. In this study, FP with random start ovarian stimulation was not associated with a delay cancer treatment in the neoadjuvant setting, so long as there was a prompt FP referral. Patients undergoing neoadjuvant chemotherapy should be informed of these findings to avoid unnecessary anxiety due to concern for delays. This study was supported by departmental research funding within the University of California, San Francisco Department of Obstetrics, Gynecology and Reproductive Sciences. There are no conflicts of interest to declare.

Back-to-back random start ovarian stimulation prior to chemotherapy results in a doubling of oocyte yield

Back-to-back random start ovarian stimulation prior to chemotherapy results in a doubling of oocyte yield

Random-start ovarian stimulation in women desiring elective cryopreservation of oocytes

The current study investigates the utility of random-start ovarian stimulation in women desiring elective oocyte cryopreservation. Women in the study cohort underwent random-start ovarian stimulation, and were subdivided based on the phase of the menstrual cycle that ovarian stimulation began, i.e. early follicular, late follicular or luteal phase. Women undergoing conventional cycle day (CD) 2/3 ovarian stimulation start were controls. A total of 1302 women were included – 859 (66.0%) conventional CD 2/3, 342 (26.3%) early follicular, 42 (3.2%) late follicular and 59 (4.5%) luteal ovarian stimulation starts. There was no difference in the demographics or baseline ovarian stimulation characteristics. The duration of ovarian stimulation (11 versus 9 days; P < 0.001) and total dosage of gonadotrophins administered (4095.5 versus 3155 IU; P < 0.001) was higher in the random-start group. The number of total and MII oocytes in the control and random-start groups was similar. A non-significant trend towards increased cycle cancellation was noted in the late follicular start group (7.1%). Study findings indicate the number of total and MII oocytes derived from random-start protocols initiated during any phase of the menstrual cycle is similar to conventional CD 2/3 ovarian stimulation start protocols in women desiring elective oocyte cryopreservation.

Long-acting recombinant follicle-stimulating hormone in random-start ovarian stimulation protocols for fertility preservation in women with cancer.

The objective of this study was to assess the effectiveness and potential benefits of the use of long-acting recombinant follicle-stimulating hormone (FSH) in a random-start protocol for fertility preservation in women with cancer. This is a retrospective before-and-after study performed between February 2013 and December 2015 in women who underwent ovarian hyperstimulation for oocyte cryobanking using a random-start approach. In the first part of the study period, the women were treated with daily recombinant FSH whereas in the second part the stimulation was initiated with long-acting recombinant FSH. The primary aim of the study was to compare the number of oocytes stored in the two study periods. In all, 140 women were ultimately selected. Compared with daily recombinant FSH, the use of the long-acting compound was associated with a reduced number of injections (12.5 ± 3.5 vs. 16.4 ± 0.3; p < 0.001) and a longer duration of stimulation (11.4 ± 1.9 vs. 10.6 ± 1.9, p = 0.01). Conversely, the number of oocytes collected (13.7 ± 9.5 vs. 11.3 ± 7.0, p = 0.10) as well as those cryopreserved (11.0 ± 8.0 vs. 9.5 ± 5.8, p = 0.21) did not differ. The use of long-acting recombinant FSH in random-start protocols for fertility preservation appears to be a valuable option.