Poor responder is a quasi-cluster of patients whose management has confounded clinicians. Luteal phase stimulation as a solution is proposed on a new principle of follicular development.
Random start of stimulation was started for women with malignancy and disorders, where limited time is available to the patient before beginning cytotoxic and gonadotoxic treatment. This has given the researchers information that luteal stimulation even when longer may be associated with a higher number of eggs retrieved.
Dr Shruti Gupta described a case report where this approach was used in an established poor responder patient with endometriosis published in International Journal of Infertility and Fetal Medicine.
Case description :
Patient X, a 34-year-old woman with 4 years of infertility was operated on laparoscopically 1 year ago where grade IV endometriosis was diagnosed, and cystectomy was performed bilaterally.Postoperatively, she underwent one cycle of superovulation and intrauterine insemination (IUI), which was unsuccessful. Thereafter, a cycle of IVF was performed elsewhere.
The stimulation was an antagonist cycle, which started with 225 IU of recombinant follicle-stimulating hormone (FSH), and 150 IU luteinizing hormone (LH). The cycle resulted in the retrieval of one egg, which did not fertilize.
The patient presented with the above history and on the investigation, her anti-Mullerian hormone (AMH) was 0.86 ng/ mL and antral follicle count (AFC) was 6 (2 + 4). The patient was planned for a luteal start of stimulation. The experimental nature of the procedure was explained to her.
Stimulation:
The patient was called on day 10/26 day of her cycle. A follicle of 14 mm was seen in her right ovary.
On further follow-up on day 14 at the follicle size of 19 mm, ovulation was triggered with inj. Triptorelin 0.2 mg.
Ovulation was confirmed on day 16 on ultrasound (USG) and progesterone levels in the blood. The AFC on day 16/D1 of stimulation was 6 (2 + 4).
Stimulation was started with urinary highly purified human menopausal gonadotropin, u-hMG 375 IU.
When the lead follicle was 12 mm in diameter and cetrorelix acetate was added.
Egg retrieval was planned at 36 hours of inj. triptorelin 0.2 mg.
She had seven oocytes retrieved, three metaphase II (MII), two metaphase I (MI), and the rest were germinal vesicle (GV).
The MII and MI oocytes (after in vitro maturation) were injected with sperms. Intracytoplasmic sperm injection (ICSI) was performed in view of previous fertilization failure.
There were three 2PN embryos at 24 hours and on day 3, (1) 8 cell grade I + (2) 8 cell grade II (20% fragmentation). The embryos were frozen for transfer at a later date because of asynchrony between the embryo and the endometrium in luteal phase stimulation.
The embryo transfer was done in a down-regulated, programmed hormone replacement cycle in view of her adenomyosis and endometriosis.
The patient was administered a depot injection of triptorelin 3.75 mg and after 3 weeks estrogen was started.
She was started on injectable progesterone intramuscularly 100 mg at an endometrial thickness of 10 mm.
The embryos on thawing were cultured to blastocysts. At 118 hours, two embryos were transferred.
Her B-hcg was 846 IU/mL and clinical pregnancy was confirmed at 6 weeks.
Outcome:
The patient developed some bleeding at 20 weeks when the lower segment placenta was made note of. The patient developed leaking at 26 weeks with heavy bleeding at 27 weeks when a lower segment cesarean was performed in view of antepartum hemorrhage and major placenta previa. The baby was a healthy 1,000 g preterm and was doing well postoperatively.
The researcher concluded , "In the present patient, the luteal phase was induced by decapeptyl trigger and confirmed by progesterone levels before starting the stimulation. We were successful in the luteal phase to obtain good quality mature oocytes in this patient with documented poor response. Researches have demonstrated the luteal phase to be equally productive in patients with neoplasia and normal responders. The usage of the luteal phase has never been demonstrated in the poor responder. Dual stimulation (shanghai protocol) has been studied in poor responders and a yield of a higher number of oocytes in the second stimulation has been achieved."
More evidence is required to improve the performance of luteal phase stimulation, e.g., it has been suggested that antagonists may not be required for controlling LH surge because of the presence of progesterone in the hormonal milieu.
Source: Gupta S. Luteal Start of Stimulation in a Case of Expected Poor Response with the Successful Outcome: A Case Report. Int J Infertil Fetal Med 2020;11(2):54–56.