In Vivo Fertilisation (INVOcell): What the Trials Show

No. “In vivo fertilisation” is a marketing name for intravaginal culture, a technique performed with a device called INVOcell. Eggs and sperm are sealed into a small gas-permeable plastic capsule together with culture medium. The capsule is placed in the vagina and left there for three to five days while fertilisation and early embryo development happen inside it. The vagina supplies warmth and gas exchange; it is standing in for a laboratory incubator, and for nothing else.

That distinction decides what matters here. The steps that make IVF invasive are unchanged:

• Ovarian stimulation with injected gonadotrophins, and monitoring
• Transvaginal egg retrieval under sedation
• An embryology laboratory to prepare the sperm, load the device, and later open it, find the embryos and grade them
• An embryo transfer, on day 5 in 95% of 526 cycles in the largest series

Lucena et al describe it plainly: fertilisation and early embryo development are carried out within a gas-permeable, air-free plastic device placed into the vaginal cavity for incubation. It is not a treatment for anyone hoping to avoid a laboratory.

Four randomised comparisons have been published, and they are all small. They point the same way on embryo quality.

• Doody 2016, 40 women randomised: IVF produced quality blastocysts from 50.6% of oocytes versus 30.7% with the device (p=0.0007). The blastocysts that were transferred did not differ significantly (97.5% versus 84.9%, p=0.09), and live birth was 60% versus 55%.
• Mitri 2015, 10 women aged 27-37 with oocytes randomised within each patient: fertilisation 68.7% with IVF versus 40.7% with the device, and significantly fewer embryos of transferable quality from the device (OR 0.47, 95% CI 0.26 to 0.87). Clinical pregnancy after transfer of device embryos was 30%.
• Aguiar 2023, eight couples per group: at day 5, conventional IVF reached 66% expanded blastocysts versus 28% with intravaginal culture, and at day 3 the IVF embryos showed better synchrony in blastomere number and quality.
• Yang Mohsin 2022, 23 women and 252 sibling oocytes split between the systems: fertilisation and good embryo quality did not differ significantly. The authors call the blastulation rate superior with INVOcell, but give it as p=0.16 — not a significant difference.

Read together: the device yields fewer good-quality embryos than an incubator, and the one trial measuring live birth found it similar, because the embryos judged good enough to transfer were comparable. That supports calling it an alternative, not an improvement.

The largest experience is descriptive, not randomised. Jellerette-Nolan et al pooled 463 patients across 526 cycles at five US centres, mainly women under 38 with AMH above 0.8 ng/mL.

• Mean cumulative live birth plus ongoing pregnancy: 29% to 53% per cycle start
• The same outcome expressed per transfer: 40% to 61%
• Mean blastocyst recovery: 19% to 34% of each oocyte loaded, across all of 526 cycles
• Several authors are employees of Ferring Pharmaceuticals, which markets INVOCELL

Those ranges are wide because they are five centres reported separately, and they are not comparable with a clinic's advertised IVF figure unless the denominator and the patient group match.

One smaller series shows why denominators matter. García-Ferreyra et al compared 24 INVO-ICSI cycles with 74 ICSI cycles and found similar pregnancy (54.2% versus 58.1%) and implantation (31.7% versus 33.6%) — but significantly more embryos were transferred per patient in the device group (2.63 versus 1.93, p<0.05). More embryos transferred raises both the per-transfer pregnancy rate and the chance of a multiple pregnancy, so those similar rates were not achieved on similar terms.

Every published use sits inside narrow entry criteria, and outside a narrower authorisation.

• Age: under 38 in the real-world series; under 38 in the Doody trial; under 40 in the sibling-oocyte study
• Ovarian reserve: AMH above 0.8 ng/mL in the real-world series, AMH 1-3 ng/mL in the Doody trial
• Body mass index: under 36 in the Doody trial, under 30 kg/m2 in the sibling-oocyte study
• Regulatory limits: INVOcell holds FDA de novo authorisation DEN150008, granted to Invo Bioscience on 2 November 2015, classified under 21 CFR 884.6165 as a class II device, product code OYO

Cooper's review states that the FDA recommends the device for minimal stimulation and up to 72 hours of culture with up to seven oocytes, while centres have used more oocytes and five days to reach blastocyst — the largest series loaded a reported maximum of 34. So much of the published experience lies beyond the cleared labelling, which is a fair question to put to a clinic offering it.

On availability in India we cannot tell you anything. No retrieved regulatory record, device registry or clinic listing establishes that it is offered here, and the FDA decision carries no legal force in India. Anyone told it is available should ask to see the approval relied on.

This literature is small, and the claims made for the device in marketing run well ahead of it.

Reasonably established:

• The device produces embryos, and pregnancies and live births follow from them
• In selected younger women with adequate ovarian reserve, reported live birth rates overlap those of conventional IVF
• It yields fewer good-quality blastocysts than an incubator in randomised comparison

Not established:

• That it produces more pregnancies or live births than conventional IVF. No retrieved study shows this, and the largest randomised comparison enrolled 40 women
• That it is cheaper in India, or anywhere. The access argument in the literature is about laboratory space, equipment and staffing in US and Brazilian settings, not about any published price
• That it is less invasive. Stimulation, retrieval and transfer are identical
• That it suits older women, low ovarian reserve, or severe male factor. Those groups were excluded from the studies
• Cumulative outcomes across several cycles. Cooper states that more data is warranted to track cumulative outcomes and to define the ideal candidate
• Obstetric and neonatal outcomes beyond a narrative review describing them as reassuring
• Any advantage for unexplained infertility specifically

The honest summary: intravaginal culture is a real, FDA-authorised alternative way to incubate embryos for a narrow group of younger patients with reasonable ovarian reserve. It is not natural conception, it is not gentler, and no retrieved evidence makes it more effective than the incubator it replaces.

• Understanding IVF: how a standard cycle works
• IUI vs IVF for couples trying to conceive
• IVF cost and insurance in India: what the law says
• Time-lapse embryo imaging: what the TILT trial found