Ovarian Stimulation Strategies for Infertility Treatment

Ovarian stimulation is a cornerstone of assisted reproductive technology, designed to recruit multiple follicles and maximise oocyte yield. Conventional protocols rely on sequential administration of gonadotrophins and pituitary suppression to synchronise follicular growth. Recent advances have introduced personalised approaches that tailor gonadotrophin dosage to individual ovarian reserve markers, improving safety and efficacy. Mild stimulation protocols, which employ lower gonadotrophin doses over shorter intervals, aim to reduce patient discomfort and the risk of ovarian hyperstimulation without compromising live-birth rates. Double-stimulation strategies, such as DuoStim, exploit follicular recruitment waves in both the follicular and luteal phases of the same menstrual cycle, thereby shortening treatment duration and enhancing oocyte accumulation for poor-prognosis patients. Random-start protocols facilitate urgent fertility preservation by initiating stimulation irrespective of menstrual phase, proving particularly beneficial for oncology patients. Emerging efforts focus on refining embryo competence through refined trigger agents and optimised luteal support, as well as exploring adjuvant therapies to improve follicular response. Collectively, these innovations underscore a shift towards flexible, patient-centred regimens that balance effectiveness, tolerability and cost-effectiveness, with global applications in fertility preservation and routine IVF practice.

Research from Nature Portfolio

Recent studies have demonstrated that young women diagnosed with gynaecological malignancies exhibit comparable ovarian response and molecular competence to control patients when undergoing ovarian stimulation. Analysis of granulosa cell steroidogenesis, gonadotrophin receptor expression and DNA damage-response pathways revealed no detrimental impact of cancer on oocyte yield, fertilisation rates or embryo development, providing reassurance for fertility preservation strategies in oncology settings.

Investigations into random-start controlled ovarian stimulation have shown that the presence of a dominant follicle or corpus luteum at initiation does not perturb follicular recruitment or oocyte yield. Comparative assessments between the active and contralateral resting ovary across different cycle phases confirmed equivalent ovarian response, supporting flexible initiation protocols that reduce treatment delay without compromising efficiency.

Ovarian Stimulation Strategies for Infertility Treatment publication trend

The graph below shows the total number of articles in ovarian stimulation strategies for infertility treatment across all publications each year (not limited to Nature Index journals).

Technical terms

Controlled ovarian stimulation (COS): The administration of exogenous gonadotrophins and suppression agents to induce the development of multiple follicles.

DuoStim: A double-stimulation protocol in which both follicular and luteal phases of the same menstrual cycle are stimulated to retrieve oocytes twice.

Luteal-phase ovarian stimulation (LPOS): Initiation of follicular recruitment and gonadotrophin treatment after ovulation, during the luteal phase.

Random-start protocol: A stimulation approach initiated at any point in the menstrual cycle, enabling urgent fertility preservation.

Ovarian sensitivity index: A ratio reflecting the number of oocytes retrieved per unit of administered gonadotrophin, indicating follicular responsiveness.

References

1. Milder is better? advantages and disadvantages of "mild" ovarian stimulation for human in vitro fertilization. Reproductive Biology and Endocrinology (2011).
2. Double Stimulation in the Same Ovarian Cycle (DuoStim) to Maximize the Number of Oocytes Retrieved From Poor Prognosis Patients: A Multicenter Experience and SWOT Analysis. Frontiers in Endocrinology (2018).
3. Influence of the starting day of luteal phase stimulation on double stimulation cycles. Frontiers in Endocrinology (2023).
4. Patients with gynecological malignancies are similar to other IVF patients without cancer for clinical and molecular reproductive parameters and DNA damage response pattern. Scientific Reports (2024).
5. The presence of dominant follicles and corpora lutea does not perturb response to controlled ovarian stimulation in random start protocols. Scientific Reports (2020).
6. Luteal phase stimulation versus follicular phase stimulation in poor ovarian responders: results of a randomized controlled trial. Reproductive Biology and Endocrinology (2020).
7. Evaluation of Ovarian Stimulation Initiated From the Late Follicular Phase Using Human Menopausal Gonadotropin Alone in Normal-Ovulatory Women for Treatment of Infertility: A Retrospective Cohort Study. Frontiers in Endocrinology (2019).